A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.
A group of telomere associated proteins that interact with TRF1 PROTEIN, contain ANKYRIN REPEATS and have poly(ADP-ribose) polymerase activity.
Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)
A genus of ciliate protozoa having a unique cursorial type of locomotion.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A genus of ciliate protozoa having a dorsoventrally flattened body with widely spaced rows of short bristle-like cilia on the dorsal surface.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A set of nuclear proteins in SACCHAROMYCES CEREVISIAE that are required for the transcriptional repression of the silent mating type loci. They mediate the formation of silenced CHROMATIN and repress both transcription and recombination at other loci as well. They are comprised of 4 non-homologous, interacting proteins, Sir1p, Sir2p, Sir3p, and Sir4p. Sir2p, an NAD-dependent HISTONE DEACETYLASE, is the founding member of the family of SIRTUINS.
Deoxyribonucleic acid that makes up the genetic material of fungi.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
Immunologically detectable substances found in the CELL NUCLEUS.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Changes in the organism associated with senescence, occurring at an accelerated rate.
The process by which a DNA molecule is duplicated.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)

Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (1/4834)

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.  (+info)

A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. (2/4834)

Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor-sensitive, mammalian senescence mechanism unrelated to telomere maintenance.  (+info)

Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability. (3/4834)

Small polydisperse circular DNA (spcDNA) is a heterogeneous population of extrachromosomal circular molecules present in a large variety of eukaryotic cells. Elevated amounts of total spcDNA are related to endogenous and induced genomic instability in rodent and human cells. We suggested spcDNA as a novel marker for genomic instability, and speculated that spcDNA might serve as a mutator. In this study, we examine the presence of telomeric sequences on spcDNA. We report for the first time the appearance of telomeric repeats in spcDNA molecules (tel-spcDNA) in rodent and human cells. Restriction enzyme analysis indicates that tel-spcDNA molecules harbor mostly, if not exclusively, telomeric repeats. In rodent cells, tel-spcDNA levels are higher in transformed than in normal cells and are enhanced by treatment with carcinogen. Tel-spcDNA is also detected in some human tumors and cell lines, but not in others. We suggest, that its levels in human cells may be primarily related to the amount of the chromosomal telomeric sequences. Tel-spcDNA may serve as a unique mutator, through specific mechanisms related to the telomeric repeats, which distinguish it from the total heterogeneous spcDNA population. It may affect telomere dynamics and genomic instability by clastogenic events, alterations of telomere size and sequestration of telomeric proteins.  (+info)

p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. (4/4834)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.  (+info)

Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. (5/4834)

To study the effect of continued telomere shortening on chromosome stability, we have analyzed the telomere length of two individual chromosomes (chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both chromosomes decreased with increasing generations of mTER-/- mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length of all chromosomes. Interestingly, the most frequent fusions found in mTER-/- cells were homologous fusions involving chromosome 2. Immortal cultures derived from the primary mTER-/- cells showed a dramatic accumulation of fusions and translocations, revealing that continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes 2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during the growth of the immortal mTER-/- cells, telomere length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER-/- cells to grow indefinitely and form tumors.  (+info)

Telomere loss in somatic cells of Drosophila causes cell cycle arrest and apoptosis. (6/4834)

Checkpoint mechanisms that respond to DNA damage in the mitotic cell cycle are necessary to maintain the fidelity of chromosome transmission. These mechanisms must be able to distinguish the normal telomeres of linear chromosomes from double-strand break damage. However, on several occasions, Drosophila chromosomes that lack their normal telomeric DNA have been recovered, raising the issue of whether Drosophila is able to distinguish telomeric termini from nontelomeric breaks. We used site-specific recombination on a dispensable chromosome to induce the formation of a dicentric chromosome and an acentric, telomere-bearing, chromosome fragment in somatic cells of Drosophila melanogaster. The acentric fragment is lost when cells divide and the dicentric breaks, transmitting a chromosome that has lost a telomere to each daughter cell. In the eye imaginal disc, cells with a newly broken chromosome initially experience mitotic arrest and then undergo apoptosis when cells are induced to divide as the eye differentiates. Therefore, Drosophila cells can detect and respond to a single broken chromosome. It follows that transmissible chromosomes lacking normal telomeric DNA nonetheless must possess functional telomeres. We conclude that Drosophila telomeres can be established and maintained by a mechanism that does not rely on the terminal DNA sequence.  (+info)

Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. (7/4834)

Mice genetically deficient for the telomerase RNA (mTR) can be propagated for only a limited number of generations. In particular, mTR-/- mice of a mixed C57BL6/129Sv genetic background are infertile at the sixth generation and show serious hematopoietic defects. Here, we show that a percentage of mTR-/- embryos do not develop normally and fail to close the neural tube, preferentially at the forebrain and midbrain. The penetrance of this defect increases with the generation number, with 30% of the mTR-/- embryos from the fifth generation showing the phenotype. Moreover, mTR-/- kindreds in a pure C57BL6 background are only viable up to the fourth generation and also show defects in the closing of the neural tube. Cells derived from mTR-/- embryos that fail to close the neural tube have significantly shorter telomeres and decreased viability than their mTR-/- littermates with a closed neural tube, suggesting that the neural tube defect is a consequence of the loss of telomere function. The fact that the main defect detected in mTR-/- embryos is in the closing of the neural tube, suggests that this developmental process is among the most sensitive to telomere loss and chromosomal instability.  (+info)

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque. (8/4834)

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.  (+info)

Using in situ hybridisation, we identified interstitial telomeric sequences in seven chromosomal translocations present in normal and in syndromic subjects. Telomeric sequences were also found at the centromeric ends of a 4p and a 4q caused by centric fission of one chromosome 4. We found that rearrangements leading to interstitial telomeric sequences were of three types: (1) termino-terminal rearrangements with fusion of the telomeres of two chromosomes, of which we report one case; (2) rearrangements in which an acentric fragment of one chromosome fuses to the telomere of another chromosome. We describe four cases of Prader-Willi syndrome with the 15q1-qter transposed to the telomeric repeats of different recipient chromosomes; (3) telomere-centromere rearrangements in which telomeric sequences of one chromosome fuse with the centromere of another chromosome. We describe two examples of these rearrangements in which not only telomeric sequences but also remnants of alphoid sequences were found ...
Figure 1. Telomere-specific FISH in prostate adenocarcinomas. A-D, examples of telomere length and cell-to-cell variability in telomere length in malignant and benign prostate tissue from men in the HPFS who were surgically treated for clinically localized prostate cancer. A, this case has strikingly variable telomere signals among the cancer cells. B, this case has extremely short telomere signals and low variability in telomere length from cancer cell to cancer cell. C, this case has weak telomere signals in the CAS cells. D, this case has strong telomere signals in CAS cells. In all of the images, the DNA is stained with DAPI (blue) and telomere DNA is stained with the Cy3-labeled telomere-specific peptide nucleic acid probe (red). Of note, the centromere DNA, stained with the FITC-labeled centromere-specific peptide nucleic acid probe, has been omitted from the image to emphasize the differences in the telomere lengths. In all panels, the asterisks highlight the cancer cells and the arrows ...
Sergei Mirkin, Tufts University, Medford, speaks on Mechanisms of genome instability mediated by interstitial telomeric sequences. This movie has been recorded by ICGEB Trieste at At... - Lyssna på S. Mirkin - Mechanisms of genome instability mediated by interstitial telomeric sequences av At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy direkt i din mobil, surfplatta eller webbläsare - utan app.
Previously, we observed that heterochromatic 4 and Y chromosomes that had experienced breakage in the male germline were frequently transmitted to progeny. Their behavior suggested that they carried functional telomeres. Here we show that efficient healing by de novo telomere addition is not unique to heterochromatic breaks. ...
Telomeres, the physical ends of chromosomes, play an important role in preserving genomic integrity. This protection is supported by telomere binding proteins collectively known as the shelterin complex. The shelterin complex protects chromosome ends by suppressing DNA damage response and acting as a regulator of telomere length maintenance by telomerase, an enzyme that elongates telomeres. Telomere dysfunction manifests in different forms including chromosomal end-to-end fusion, telomere shortening and p53-dependent apoptosis and/or senescence. An important shelterin-associated protein with critical role in telomere protection in human and mouse cells is the catalytic subunit of DNA-protein kinase (DNA-PKcs). DNA-PKcs deficiency in mouse cells results in elevated levels of spontaneous telomeric fusion, a marker of telomere dysfunction, but does not cause telomere length shortening. Similarly, inhibition of DNA-PKcs with chemical inhibitor, IC86621, prevents chromosomal end protection through mechanism
Telomeres are the outermost parts of linear chromosomes. They consist of tandemly repeated non-coding short nucleotide sequences (TTAGGG in all vertebrates), in humans spanning over the last 2 to 15 kilobase pairs of the chromosome. Due to the end-replication problem, telomeres shorten with each cellular division. A critically short telomere will trigger the cell to enter a state of cellular senescence or to apoptose. The rate of telomere shortening can be accelerated by factors such as oxidative stress and inflammation. Taken together, this contributed to making telomere length a candidate biomarker of health and aging. Studies have shown that leukocyte telomere length progressively shortens with age, and that it independent of age is associated with age-related morbidity, lifestyle factors, and mortality. This thesis was aimed at exploring the relationships of leukocyte telomere length with various functional and structural attributes of the brain.. In Paper I, telomere length was shown to be ...
Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere ...
The SNP rs398652 on 14q21 and several other promising genetic variants were associated in our GWAS with telomere length in leukocytes. We then found that rs398652 was also associated with reduced bladder cancer risk. This SNP is located within the region of 14q that has a high linkage with leukocyte telomere length and is fewer than 450 kb from a microsatellite marker (D14S285) shown to have a very high logarithm (base 10) of odds (LOD) of approximately 3.5 for linkage with telomere length in a previous genetic linkage analysis (27). Furthermore, our mediation analysis to dissect the relationship between rs398652, telomere length, and bladder cancer risk suggests that the association of this SNP with bladder cancer is partially mediated by telomere length.. Telomere shortening and telomerase activation are critical early events of tumorigenesis. Results from a number of epidemiologic studies suggest that shorter telomere length in leukocytes is associated with increased cancer risks for several ...
Human telomeres can be maintained by the enzyme telomerase, which catalyses the addition of telomere repeats, or by the Alternative Lengthening of Telomeres (ALT) mechanism, which is recombination based. Recently, knockout mouse cell lines have indicated that epigenetic modifications associated with telomeric and subtelomeric chromatin, including DNA methylation, Histone 3 Lysine 9 (H31K9) trimethylation and Histone 4 Lysine 20 (H4K20) trimethylation, play an important role in influencing the choice of telomere maintenance mechanism. In this thesis, the levels of these modifications were studied in telomeric chromatin and in the telomere adjacent chromatin of the short arm of the human sex chromosomes (XpYp) in a panel of six human cell lines utilising different telomere maintenance mechanisms. In marked contrast to mouse models, no relationship was found between the level of any of these modifications and telomere maintenance pathway. This may indicate that the role such marks play at telomeres ...
The protective caps on chromosome ends - known as telomeres - consist of DNA and associated proteins that are essential for chromosome integrity. A fundamental part of ensuring proper telomere function is maintaining adequate length of the telomeric DNA tract. Telomeric repeat sequences are synthesized by the telomerase reverse transcriptase, and, as such, telomerase is a central player in the maintenance of steady-state telomere length. Evidence from both yeast and mammals suggests that telomere-associated proteins positively or negatively control access of telomerase to the chromosome terminus. In yeast, positive regulation of telomerase access appears to be achieved through recruitment of the enzyme by the end-binding protein Cdc13p. In contrast, duplex-DNA-binding proteins assembled along the telomeric tract exert a feedback system that negatively modulates telomere length by limiting the action of telomerase. In mammalian cells, and perhaps also in yeast, binding of these proteins probably ...
The CDC13 gene has previously been implicated in the maintenance of telomere integrity in Saccharomyces cerevisiae. With the use of two classes of mutations, here it is shown that CDC13 has two discrete roles at the telomere. The cdc13-2est mutation perturbs a function required in vivo for telomerase regulation but not in vitro for enzyme activity, whereas cdc13-1ts defines a separate essential role at the telomere. In vitro, purified Cdc13p binds to single-strand yeast telomeric DNA. Therefore, Cdc13p is a telomere-binding protein required to protect the telomere and mediate access of telomerase to the chromosomal terminus.. ...
Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular
Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular
Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths...
a) Mammalian telomeres consist of tandem repeats of the TTAGGG sequence that are bound by the shelterin-telosome protein complex. Adjacent to telomeres are the subtelomeric regions, which are also rich in repetitive DNA. (b) In addition to shelterin, mammalian telomeres also contain nucleosomes that show histone modifications characteristic of heterochromatin domains. In addition, subtelomeric DNA is heavily methylated. These chromatin modifications at telomeres and subtelomeres have been shown to negatively regulate telomere length and telomere recombination. TriM, trimethyl. Image and legend from Telomere length, stem cells and aging.. You can also have a look at the diagrams related to telomere extension in my 2011 blog entry The epigenetic regulation of telomeres.. Shortened telomeres is only one of a number of factors that can contribute to cellular senescence, and may often be a downstream effect of such factors.. Apostles of telomere-extending would lead us to believe that cell ...
Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed. Average relative telomere lengths were measured in cord blood (n = 743) and placental tissue (n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIRONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths. Maternal age was 29.1 years (range, 17-44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m2. Decline in newborn
Almost 12 years ago, an evolutionary theory based on intergenerational telomere erosion was introduced [8] and was widely covered by the press [11, 12]. In 2011, based on published data on human telomere length inheritance, I refined my theoretical framework and located the source of human intergenerational telomere erosion in the female germline [6, 7, 10]. According to this model, telomeres in the testes of elderly males are longer than those in young males because the seniors are members of a previous generation (=birth-cohort effect) and therefore skipped, on average, one female-based intergenerational telomere loss. In 2014, I further developed the model of telomere-driven macroevolution and presented a complete biological framework for the old European model of saltatory evolution of nonadaptive characters [6].. In agreement with this theoretical model, a high-profile study, published in the August issue of Aging Cell in 2015, finally confirmed the long-awaited birth-cohort effect on ...
Telomere length analysis of donor-derived bone marrow cells (Fig. 3) and HSCs (Fig. 4) shows substantial telomere shortening during serial HSC transplantation. The difference in mean TRF length (ΔTRF) of bone marrow cells after one round of HSC transplantation is ∼1.5 kb (Fig. 3 B). This agrees reasonably well with the predicted reduction in telomere size assuming that ΔTRF is mainly due to the minimum number of extra population doublings (∼12-13) required for expansion of the fraction of the transplanted HSC population which engraft to the size of the HSC pool in adult mice (∼3-5 × 104 cells; references 3, 4), and that the rate of telomere shortening during division of the transplanted HSCs is 50-100 bp per population doubling, as observed for other mouse cells 14,39,40. However, the extent of telomere shortening during the second round of HSC transplantation (ΔTRF ≈ 5.5 kb) is considerably greater than ΔTRF during the first round of transplantation (Fig. 3). One possible ...
The results described in this study provided evidences that SYUIQ5, a Gquadruplex ligand, potently inhibited the proliferation and induced telomere DNA damage and autophagy in CNE2 and HeLa cancer cells in vitro. TRF2 delocalized from telomeres after SYUIQ5 treatment and was further degraded by proteasomes. In addition, overexpression of TRF2 prevented SYUIQ5-mediated cell death. ATM was also activated and involved in SYUIQ-5-induced telomere DNA damage response and autophagy. Furthermore, ATG5 knockdown attenuated the cytotoxicity of SYUIQ-5 in CNE2 and HeLa cells.. Telomeres are capable of forming guanine quadruplex (G4) structures on the G-rich strand, and the ligands that interact with G-quadruplex are recognized as promising anticancer agents by interfering with telomere conformation and telomere elongation. These compounds were first evaluated as telomerase inhibitors and induced telomere shortening and senescence. Recently, it was observed that G-quadruplex ligands induced a short-term ...
Debido al estado altamente heterocromatinizado del telómero se pensaba que el final de los cromosomas no era transcrito. Sin embargo, hace una década se demostró que los telómeros se transcriben en una familia de lncRNAs denominados Telomeric repeat-containing RNA o TERRA. En los últimos años, un gran número de funciones diferentes han sido asociadas a estos transcritos. Sin embargo, la falta de modelos genéticos KO para TERRA ha impedido confirmar estas funciones en sistemas celulares. La falta de modelos se debe mayoritariamente a que su origen subtelomérico no está claro. En humanos, los estudios más recientes han propuesto que TERRA se podría transcribir de 18 loci diferentes, dificultando en gran medida la generación de células KO para TERRA. Uno de los principales objetivos de mi tesis, ha sido identificar los posibles loci de TERRA humanos, con el objetivo de generar células humanas KO para TERRA. Primero evaluamos los 18 loci previamente descritos, encontrando que el 80% ...
In human cells, homologous recombination (HR) provides an accurate mechanism for the repair of DNA double-strand breaks caused by replication fork breakdown or DNA damaging agents. HR also plays a role in the maintenance of eukaryotic telomeres; cells defective in the recombinational repair proteins RAD51D or RAD54 exhibit telomere shortening and end-to-end chromosome fusions. Here we discuss the way in which HR contributes to telomere protection and elongation in mammalian cells. Understanding the mechanisms by which HR promotes telomere maintenance has important implications for genomic stability and tumorigenesis.
Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity
4. The Curious Case of Skeletal Muscle Telomere Biology in Humans Skeletal muscle has unique telomere biology when compared to other tissues. Skeletal muscle consists of a syncytium of multinucleated muscle fibers that are postmitotic; thus, telomere length should remain stable in this population of nuclei, with the rare exception of DNA damaging stimuli [89]. In addition to myonuclei, single-nucleated populations of cells, of which the best described are satellite cells, also populate skeletal muscle [90]. Satellite cells are muscle precursor cells (i.e., adult stem cells) that are quiescent unless induced to divide by external stressors, such as contraction-induced or injury-induced muscle damage [90]. When induced to divide, satellite cells divide asymmetrically, with one daughter cell incorporating into the damaged muscle fiber and the other daughter cell returning to replenish the satellite cell pool [90]. Skeletal muscle telomere dogma states that when a muscle precursor cell is induced to ...
It is not the length of telomeres per se that protects against loss of chromosome end function, but the ability to maintain sufficient length to form a functional telomere cap. Although equilibrium telomere lengths vary dramatically between yeast, mice and humans, they share a dosage-sensitive balance between telomere loss and replenishment. In heterozygous mTert mice that have been bred for many generations, we propose that initial telomere attrition followed by eventual recovery reflects such a length-dependent equilibrium. In S. cerevisiae and humans, long telomeres inhibit telomerase access owing to cis-inhibition by telomere-bound factors such as Rif1/Rif2 and TRF1/TRF2, respectively (Smogorzewska and de Lange, 2004; Hug and Lingner, 2006). Once telomeres become short, the dosage of telomere-bound factors is reduced, leading to loss of cis-inhibition and a switch to a telomerase-extendible state (Smogorzewska and de Lange, 2004; Hug and Lingner, 2006). Upon telomere shortening, murine cells ...
We measured the effects of long-term NRTI and NNRTI exposure on telomere length maintenance using the HT29 human colorectal adenocarcinoma cell model (Table 2). HT29 has robust telomerase activities, as measured by the PCR-based telomerase activity assay [31]. HT29 cells were treated with a minimum of two concentrations of NRTIs or NNRTIs. Cell proliferation and growth rate was monitored continuously. Long-term treatment of HT29 cells with AZT is known to cause telomere length attrition [9,10,11,13]. Using the terminal restriction fragment (TRF) assay, we confirmed substantial inhibitory effects of AZT on telomere length maintenance in HT29 cells (Figure 6A and 6B). Mean telomere length was determined as a weighted average with reference to DNA standards. Figure 7. Continuous treatment of HT29 cells with the adenosine analogs TDF and ddI causes observable telomere shortening. A. TRF blots of untreated (left), TDF-treated (right) HT29 cells. PDL at which TRF was analyzed is shown above each lane. ...
Telomeres are ribonucleoprotein structures at the end of chromosomes composed of telomeric DNA, specific-binding proteins and noncoding RNA (TERRA). Despite their importance in preventing chromosome instability, little is known about the crosstalk between these three elements during the formation of the germ line. Here, we provide evidence that both TERRA and the telomerase enzymatic subunit (TERT) are components of telomeres in mammalian germ cells. We found that TERRA co-localizes with telomeres during mammalian meiosis and that its expression progressively increases during spermatogenesis, until the beginning of spermiogenesis. While both TERRA levels and distribution would be regulated in a gender-specific manner, telomere-TERT co-localization appears to be regulated based on species-specific characteristics of the telomeric structure. Moreover, we found that TERT localization at telomeres is maintained all through spermatogenesis as a structural component without affecting telomere ...
Single-stranded DNA-dependent ATP-dependent helicase. Involved in non-homologous end joining (NHEJ) DNA double strand break repair. DNA-binding is sequence-independent but has a high affinity to nicks in double-stranded DNA and to the ends of duplex DNA. Binds to naturally occurring chromosomal ends, and therefore provides chromosomal end protection. Appears to have a role in recruitment of telomerase and CDC13 to the telomere and the subsequent telomere elongation. Required also for telomere recombination to repair telomeric ends in the absence of telomerase. KU70, of the KU70/KU80 heterodimer, binds to the stem loop of TLC1, the RNA component of telomerase. Involved in telomere maintenance. Interacts with telomeric repeats and subtelomeric sequences thereby controlling telomere length and protecting against subtelomeric rearrangement. Maintains telomeric chromatin, which is involved in silencing the expression of genes located at the telomere. Required for mating-type switching.
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
Mutations accumulate as a result of DNA damage and imperfect DNA repair machinery. In higher eukaryotes the accumulation and spread of mutations is limited in two primary ways: through p53-mediated programmed cell death and cellular senescence mediated by telomeres. Telomeres shorten at every cell division and cell stops dividing once the shortest telomere reaches a critical length. It has been shown that the rate of telomere attrition is accelerated when cells are exposed to DNA damaging agents. However the implications of this mechanism are not fully understood. With the help of in silico model we investigate the effect of genotoxic stress on telomere attrition and apoptosis in a population of non-identical replicating cells. When comparing the populations of cells with constant vs. stress-induced rate of telomere shortening we find that stress induced telomere shortening (SITS) increases longevity while reducing mutation rate. Interestingly, however, the effect takes place only when genotoxic
TY - JOUR. T1 - Telomere length dynamics and chromosomal instability for predicting individual radiosensitivity and risk via machine learning. AU - Luxton, Jared J.. AU - McKenna, Miles J.. AU - Lewis, Aidan M.. AU - Taylor, Lynn E.. AU - Jhavar, Sameer G.. AU - Swanson, Gregory P.. AU - Bailey, Susan M.. N1 - Funding Information: Funding: This research was funded by the Colorado Office of Economic Development and International Trade (OEDIT) Advanced Industry (AI) Bioscience Proof of Concept (POC) award program, Colorado State University (CSU) Ventures. Graduate student fellowships awarded by CSUs Program of Research and Scholarly Excellence (PRSE), and the Cancer Biology and Comparative Oncology (CB&CO) PRSE to support quantitative Cell and Molecular Biology (qCMB) studies, are also gratefully acknowledged. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.. PY - 2021/3. Y1 - 2021/3. N2 - The ability to predict a cancer patients response to radiotherapy and risk ...
The TeloYears test is not intended for screening, diagnosing, treating or preventing diseases or medical conditions. The TeloYears genetic test may indicate the possibility of identifying a rare telomere syndrome associated with extremely shorter or longer average telomere length (ATL). In these rare cases, further testing and consultation with a doctor to rule in or rule out a telomere syndrome is recommended. The test is available for individuals between the ages of 20 to 80 within the United States, except for the states of Maryland and New York. The information provided by the TeloYears test should not be used to replace medically appropriate screening tests recommended based upon actual age or other risk factors, nor should the information be used to make decisions about diagnosis or treatment of diseases or medical conditions. The Telomere Diagnostics lab is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) as qualified to perform high complexity clinical ...
Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related
Understanding the molecular processes that drive cellular replicative senescence is critical to understanding human longevity. Much attention has focused on telomere length as a determinant of replicative capacity (1). Telomeres are nucleoprotein structures composed of species-specific tandemly repeated, G-rich DNA sequences that cap and protect chromosome ends from nucleolytic attack and degradation (2). Telomeres also conceal linear chromosome ends from inappropriate attempts at double-strand break (DSB) repair that might otherwise join chromosomes end-to-end. The preservation of natural chromosome ends and the rejoining of broken DNA ends, both of which are essential for preserving genomic integrity, rely on a common subset of proteins (3), and both decline with advancing age (4, 5).. The G-rich nature of telomeric DNA renders it susceptible to G-quadruplex formation, oxidative damage, and alkylation by electrophiles (6). Telomeres are also unique in their chromatin composition, being bound ...
The Patient Telomere Score is calculated based on the patients average telomere length in peripheral whole blood cells. This average is then compared to telomere lengths from a population sample in the same age range as the patient to determine the patients percentile score. What do the results mean to the patient and the doctor? Cellular attrition by analyzing the rate at which changes in average Telomere length occur over time. Cells are being lost and replaced. (Cellular attrition) What are the nutritional implications on telomere length and repair? An inflammatory diet, or one that increases oxidative stress, will shorten telomeres faster. This includes refined carbohydrates, fast foods, processed foods, sodas, artificial sweeteners, trans fats and saturated fats. A diet with a large amount and variety of antioxidants that improves oxidative defense and reduces oxidative stress will slow telomere shortening. Consumption of 10 servings of fresh and relatively uncooked fruits and vegetables, ...
Why is this important In embryonic cells (and some stem cells), an enzyme called telomerase rebuilds the telomere so that the cells can keep dividing. Over time, this telomerase dwindles and eventually the telomere shortens and the cell becomes inactive. In cancer cells, the telomerase enzyme keeps rebuilding telomeres long past the cells normal lifetime. The cells become immortal, endlessly dividing, resulting in a tumor. Researchers estimate that telomere maintenance activity occurs in about 90% of human cancers. But the mechanism by which this maintenance takes place is not well understood. The researchers discovered that the RNA in the telomere is regulated by a protein in the telomerase enzyme. Their discovery may thus uncover key elements of telomere function ...
TY - JOUR. T1 - Telomere length in peripheral blood leukocytes and risk of renal cell carcinoma. AU - Park, Jong Y.. AU - Luu, Hung N.. AU - Park, Hyun Y.. AU - Lin, Hui Yi. AU - Radlein, Selina. AU - Di Pietro, Giuliano. AU - Yeo, Chang Dong. AU - Kim, Seung Joon. AU - Kang, Nahyeon. AU - Antwi, Samuel. AU - Sexton, Wade J.. AU - Spiess, Philippe E.. AU - Dickinson, Shohreh. AU - Parker, Alexander. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Background: Telomeres are essential for chromosomal stability and may play a key role in carcinogenesis. Telomere length is suggested as a tentative biomarker of risk for renal cell carcinoma (RCC). However, results of previous association studies between telomere length and risk for RCC are inconsistent. Methods: We evaluated RCC risk in relation to peripheral blood leukocyte telomere length using a hospital-based case-control study of 169 RCC cases and 189 controls. Cases were histologically-confirmed RCC patients who were treated at the Moffitt Cancer Center ...
An SGA approach to discover cdc13-1ts supressors. Telomeres, the DNA-protein complexes at the end of eukaryotic chromosomes, are essential for chromosomal stability. In yeast, the telomeric single-strand binding protein Cdc13p has multiple important roles related to telomere maintenance: (1) telomericcapping--protection of telomeres by forming complexes with yKu70/80 and with Stn1p/Ten1p; (2) positive regulation of telomere replication via interaction with Est1p, which is a part of telomerase; (3) negative regulation of telomerase by the recruitment of telomere elongation suppressors Stn1p and Ten1p. In an attempt to identify genes that are involved in the deleterious outcome of an absence of Cdc13p, we screened the yeast gene knock-out library for genes that could suppress the growth defect of cdc13-1 cells at 33ê C. For this purpose, we performed an SGA array experiment. We scored for the ability of double mutant haploids to grow at 33ê C. Eventually, we hoped to find the elusive genes ...
Laure Crabbe, Ramiro E. Verdun, Candy I. Haggblom, and Jan Karlseder http://sageke.sciencemag.org/cgi/content/abstract/2004/50/or22 Abstract: Science 306, 1951-1953 (2004).. Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.. [Abstract/Full Text]. ...
We have isolated STN1, an essential Saccharomyces cerevisiae gene, as a suppressor of the cdc13-1 mutation. A synthetic lethal interaction between a temperature-sensitive mutant allele of STN1, stn1-13, and cdc13-1 was observed. Stn1 and Cdc13 proteins displayed a physical interaction by two-hybrid analysis. As shown previously for cdc13-1, stn1-13 cells at the restrictive temperature accumulate single-stranded DNA in subtelomeric regions of the chromosomes, but to a lesser extent than cdc13-1 cells. In addition, both Cdc13 and Stn1 were found to be involved in the regulation of telomere length, mutations in STN1 or CDC13 conferring an increase in telomere size. Loss of Stn1 function activated the RAD9 and MEC3 G2/M checkpoints, therefore confirming that DNA damage is generated. We propose that Stn1 functions in telomere metabolism during late S phase in cooperation with Cdc13 ...
Telomeres, which are found at the end of eukaryotic linear chromosomes, are essential for chromosome maintenance and genomic stability (1). Mammalian telomeres are composed of repetitive d-(TTAGGG) sequences and telomere-specific shelterin complex proteins, which protect the chromosome ends from being recognized as DNA damage and preventing end-to-end chromosomal fusions (2). The shelterin proteins (TRF1, TRF2, POT1, TIN2, TPP1, and RAP1) form a protective complex that is present at telomeres throughout the cell cycle (3). Because of the end-replication problem, oxidative damage and other replication-associated end-processing events, telomeres progressively shorten with each round of DNA replication in normal somatic cells (4). The ribonucleoprotein enzyme complex telomerase counteracts telomere shortening by adding hexameric telomeric DNA (TTAGGG) repeats to the end of linear chromosomes in cancer cells but only partially counteracts progressive telomere shortening in some normal human ...
Figure 3. Mutations in STN1 result in abnormal telomere phenotypes. (A) DNA samples, prepared from PBLs of patient P1, her heterozygous father (F1), and a noncarrier sibling (S1) and patient P2, his heterozygous mother (M2), and two independent control samples (C), were analyzed by in-gel hybridization. Duplicated lanes were electrophoresed in the same gel, and then separated and hybridized to a G-rich or C-rich telomeric probe, as indicated above the panels. After native hybridization to detect single-stranded telomeric DNA (top), the gels were denatured and rehybridized with the same probes to detect the overall duplex telomeric DNA (bottom). Treatment with exonuclease I is indicated above the lanes. (B) Graphic illustration of the mean telomere length for the patients and their family members, calculated based on the following number of independent measurements of four in-gels and two Southern analyses: P1:6, M1:3, F1:3, S1:3, P2:9, M2:3, F2:1, C1:2, and C2:3. (C) Graphic illustration of the ...
Osteoarthritis (OA) and osteoporosis (OP) are associated skeletal pathologies and have as a distinct feature the abnormal reconstruction of the subchondral bone. OA and OP have been characterized as age‑related diseases and have been associated with telomere shortening and altered telomerase activity (TA). This review discusses the role of telomeres and telomerase in OA and OP pathologies and focuses on the usability of telomere length (TL) and the rate of telomere shortening as potential disease biomarkers. A number of studies have demonstrated that telomere shortening may contribute to OA and OP as an epigenetic factor. Therefore, it has been claimed that the measurement of TL of chondrocytes and/or peripheral blood cells may be an appropriate marker for the evaluation of the progression of these diseases. However, there is a need to be perform further studies with larger cohorts, with the aim of obtaining objective results and a better understanding of the association between TL, ...
POT1 is one of the six core components of the human telomeric protein complex (reviewed in de Lange, 2005). This complex is composed of TRF1, TRF2, TIN2, TPP1 (previously known as PIP1, PTOP, or TINT1), Rap1, and POT1, which are thought to fulfill the two main functions of telomeres: the recruitment and regulation of telomerase, and the protection of chromosome ends. Defects in telomere protection activate the DNA damage response, leading to a DNA damage signal and inappropriate DNA repair reactions at chromosome ends. The cell cycle arrest resulting from telomere dysfunction is thought to be responsible for the finite lifespan of human cells lacking telomerase.. The current challenge is to understand how the telomeric complex protects chromosome ends from being recognized as sites of DNA damage. One approach is to define which repair and signaling pathways are repressed at natural chromosome ends by studying the events at dysfunctional telomeres. This approach has shown that chromosome ends are ...
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5-TTAGGG-3 repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5-TTAGGG-3 sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B
Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1 years). Participants completed a health questionnaire and had blood samples collected for immune-endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up (β = 0.98, p =
Depletion of hematopoietic stem cell reserves, expressed as the shortening of leukocyte telomere length (LTL), sets a limit on longevity and increases the risk...
Objective:: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods:: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results:: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of ...
TELOMERES are nucleoprotein complexes at the termini of linear eukaryotic chromosomes that perform a critical role in maintaining genome stability. At the DNA level, telomeres typically comprise long double-stranded tracts of a repetitive GT/CA-rich sequence, terminating in a short single-stranded 3′ overhang that corresponds to the strand bearing the G-rich repeats. A large number of proteins associate with the telomere repeats to form a structure that allows telomeres to act as caps that protect chromosome ends from degradation and illegitimate end-to-end fusions. Chromosomes are considered capped if they preserve the physical integrity of the telomere while allowing cell division to proceed (Blackburn 2000). Proteins that bind to the duplex portion of telomeres, such as TRF1 and TRF2 in mammalian cells and Rap1p in Saccharomyces cerevisiae, as well as proteins that bind the single-strand overhang, such as POT1 in mammalian cells and Cdc13p in S. cerevisiae, are essential for proper ...
CONTEXT: Both leukocyte telomere length and IGF-I are associated with the aging process. A previous in vitro study suggested that IGF-I may modulate telomerase activity in white blood cells, but little is known whether these two systems interact in vivo. PATIENTS AND METHODS: Leukocyte telomere length was determined using a quantitative PCR assay in 2744 elderly men (mean age 75.5 yr, range 69-81 yr) included in the population-based Osteoporotic Fractures in Men-Sweden study. Serum IGF-I concentration was measured using RIA. RESULTS: Subjects with a leukocyte telomere length in the lowest tertile group had lower serum IGF-I concentration than subjects in the two tertile groups with longer telomere lengths (P = 0.005). Logistic regression analyses showed that a higher serum IGF-I concentration was associated with a significantly reduced risk of having a leukocyte telomere length in the lowest tertile group and also after adjustment for multiple covariates (P , 0.01). Multivariate linear ...
Objectives: Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc).. Methods: Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n = 43; age range 37-80 years) and a control population (n = 107; age range 21-65 years).. Results: Telomere lengths in lcSSc subjects were longer than controls (p,0.001), did not show age-related telomere erosion and differed significantly from age-matched controls only after 50 years of age (p,0.001).. Conclusions: This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ...
Abstract Bachground The premature ovarian failure (POF) is a reason of infertility that affects about 1-4% of women before age 40. The importance of telomeres length in different diseases has been explored before. This study examines the association between the relative telomere length and idiopathic POF in a group of Iranian women. Methods The blood genomic DNA was extracted from 40 idiopathic POF patients (case group) and 40 fertile women (control group). The relative telomere length (RTL) was evaluated by quantitative Real-Time PCR using specific telomeric primers. RTL was calculated as T (telomere)/S (single copy gene) ratio and compared between infertile and fertile groups. Results A strong association was considered between telomere size and idiopathic premature ovarian failure. In patients the relative telomere length showed to be significantly longer than those of control group (P , .05, 95% CI). Conclusion Our findings demonstrate a possible relationship between telomere lengthening ...
Consumption of sugar-sweetened beverages (SSBs) is linked to increased risks of metabolic disease, but the biological mechanisms underlying this association are still under investigation. Leukocyte telomere length maintenance underlies healthy cellular aging, and may provide a link between SSB consumption and risk of disease. Given the known effects of SSBs on oxidative stress and insulin resistance, we examined the associations between sugar-sweetened beverage, diet soda, and fruit juice consumption, and leukocyte telomere length in 5,309 healthy adults with no prior history of diabetes or cardiovascular disease, using data from the 1999-2002 National Health and Nutrition Surveys (NHANES). We hypothesized that beverages with high sugar content would be most detrimental to cellular aging. Leukocyte telomere length was assayed from DNA specimens collected from adult NHANES participants. Diet was assessed using 24-hour dietary recalls. Because 24-hour dietary recalls may not accurately reflect ...
TY - JOUR. T1 - Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. AU - Ding, Jianzhong. AU - Hayashi, Mariko K.. AU - Zhang, Ying. AU - Manche, Lisa. AU - Krainer, Adrian R.. AU - Xu, Rui Ming. PY - 1999/5/1. Y1 - 1999/5/1. N2 - Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 Å resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal ...
Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that cause tissue degeneration during ageing. Cancer, with incidence rates greatly increasing with age, is characterized by short telomere lengths and high telomerase activity. To study the roles of telomere dysfunction and telomerase reactivation in ageing and cancer, the protocol shows how to generate two murine inducible telomerase knock-in alleles 4-Hydroxytamoxifen (4-OHT)-inducible TERT-Estrogen Receptor (mTERT-ER) and Lox-Stopper-Lox TERT (LSL-mTERT). The protocol describes the procedures to induce telomere dysfunction and reactivate telomerase activity in mTERT-ER and LSL-mTERT mice in vivo. The representative data show that reactivation of telomerase activity can ameliorate the tissue degenerative phenotypes induced by telomere dysfunction. In order to determine the impact of telomerase reactivation on tumorigenesis, we generated prostate ...
TY - JOUR. T1 - Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts. AU - Cui, Wei. AU - Aslam, Samena. AU - Fletcher, Judy. AU - Wylie, Diana. AU - Clinton, Michael. AU - Clark, A John. PY - 2002. Y1 - 2002. N2 - Telomere shortening and lack of telomerase activity have been implicated in cellular senescence in human fibroblasts. Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. However, telomere length is not maintained in all cell lines, even though in vitro telomerase activity is restored in all of them. Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability. By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length. The shorter telomere lengths and the extent of karyotypic ...
Schizophrenia is a complex neurodevelopmental disorder characterized by mental dysfunction in multiple domains of the brain (46). Previous studies have shown lower telomere length in patients with schizophrenia and paranoid schizophrenia compared to control groups (47,48). Patients suffering from paranoid schizophrenia, who were under anti-psychotics medication had slightly decreased leukocyte telomere length. In addition, telomere length analysis of paranoid schizophrenic patients revealed that response to treatment influences telomere length with poor responders having the shorter telomeres (49). By contrast, other authors have shown that the poor responders had the shortest terminal restriction fragments (TRFs) which was inversely associated with age. Furthermore, Fernandez-Egea et al (19), who included both men and women, showed that the whole psychosis group had decreased telomere content compared to the control group and that both men and women had the same telomere content. However, when ...
Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase
Telomeres are the caps that form ends of human chromosomes to protect the DNA strands from becoming damaged. The word telomere comes from the Greek words telos (end) and meros (part). Throughout our lives, our cells need to replenish by copying themselves (also known as cell division). The downside of this process is that the telomeres shorten each time a cell copies itself. Eventually, when the telomeres get so short that cant do their job, cells will age and stop functioning properly. This essentially means that telomeres are our cells biological clocks - their length represents our biological age as opposed to our chronological age.. Although the shortening of telomeres can suppress tumors, there is growing evidence that telomere shortening also restricts stem cell function, organ maintenance, and regeneration. During aging and disease, telomere shortening can also increase risk of cancer. ...
Electrochemical behavior of the anticancer doxorubicin hydrochloride( DOX) and the interaction of DOX with human telomere DNA were investigated by cyclic voltammetry in aqueous medium using p H 6. 0 PBS buffer. The results showed that a pair of reversible oxidation- reduction peaks were observed at- 0. 585 V and- 0. 638 V in p H 6. 0 PBS buffer. There existed excellent linearities between oxidation peak current and concentration of DOX in the ranges of 0. 03- 0. 8 μmol/L and0. 8- 10 μmol/L by linear sweep voltammetric method. Detection limit( S/N = 3) was 0. 01 μmol /L. The relative standard deviations of the oxidation peak current obtained from 11 determinations of the same solutions containing 0. 5 μmol/L DOX were 3. 5%. The oxidation peak current of DOX gradually decreased with the adding of various concentrations of human telomere DNA,due to interaction of DOX with human telomere DNA. The binding ratio was calculated to be 1 ∶ 1 and the binding equilibrium constant was 1. 11 × 103 L/mol.
In this study, we identify decreased dyskerin protein levels as a novel mechanism of disease in X-linked DC. In affected individuals, despite the presence of an intact coding sequence, decreased dyskerin levels were associated with reduced hTR stability and telomere shortening. Knockdown of dyskerin levels has been previously shown to decrease hTR levels in cancer cell lines,39 40 although its consequences on telomere length have not been examined. Our data indicate that intact dyskerin levels, and not only protein sequence, are essential for in vivo telomere maintenance, and this defect is sufficient to cause premature mortality due to telomere mediated disease. In half of X-linked DC families, the mechanism of disease is not known. Our data, if replicated in larger cohorts, would suggest that quantitation of dyskerin protein levels can complement sequencing of the DKC1 gene, and decreased levels of dyskerin, measured by sensitive methods, can identify male carrier status in a subset of ...
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative ...
in Anticancer Research (2008), 28(5c), 3257-3258. Telomeres consist of protein complexes and repeated TTAGGG double strand DNA sequences ended by a 3 single strand DNA of the same sequence. Progressive telomere shortening is observed in vitro upon ... [more ▼]. Telomeres consist of protein complexes and repeated TTAGGG double strand DNA sequences ended by a 3 single strand DNA of the same sequence. Progressive telomere shortening is observed in vitro upon cell divisions and with ageing in vivo. At a critical telomere length, shortened telomeres trigger a permanent growth arrest known as replicative senescence. Telomerase is an RNA-dependent DNA polymerase that extends telomeres by adding TTAGGG repeats. It consists of a functional RNA component (hTR) which serves as template and a catalytic protein (hTERT) with reverse transcriptase activity. The expression of hTERT alone is sufficient for the immortalisation of cells. Telomerase is highly expressed in tumor cells but at very low level ...
Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in
Telomeres, the natural ends of linear eukaryotic chromosomes, are essential for chromosome stability. Because of the nature of DNA replication, telomeres require a specialized mechanism to ensure their complete duplication. Telomeres are also capable of silencing the transcription of genes that are located near them. In order to identify genes in the budding yeast Saccharomyces cerevisiae that are important for telomere function, a screen was conducted for genes that, when expressed in high amounts, would suppress telomeric silencing. This screen lead to the identification of the gene TLC1 (telomerase component 1). TLC1 encodes the template RNA of telomerase, a ribonucleoprotein required for telomere replication in a variety of organisms. The discovery of TLC1 confirms the existence of telomerase in S. cerevisiae and may facilitate both the analysis of this enzyme and an understanding of telomere structure and function. ...
Author Summary The enzyme complex telomerase, with its two main components telomerase reverse transcriptase and telomerase RNA, plays an important role in telomere maintenance. Perturbation of telomere length regulation can ultimately result in cellular senescence (telomere shortening) and is also observed in tumor cells (increased telomere maintenance). Recent studies suggest telomerase RNAs can function independently of the telomerase complex and promote tumor development independently of telomere maintenance. Here we demonstrate that vTR, a herpesvirus-encoded telomerase RNA, serves two distinct functions in MDV-induced tumor formation. vTR has its first function early after infection, when it is part of the telomerase complex and contributes to the survival of rapidly dividing transformed cells. The second function of vTR is independent of telomerase action and essential for formation of solid lymphomas and metastasis. This latter function is likely a consequence of vTR-mediated gene regulation that
PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in ...
Telomeres are important protein-DNA structures at the ends of linear eukaryotic chromosomes that are necessary for genome integrity. Telomeres are maintained by intermittent action of telomerase. I explored the kinetics of telomere length homeostasis in the model plant Arabidopsis thaliana by crossing wild type plants to different generations of telomerase deficient plants, and then analyzing telomere length in the resulting progeny. Unexpectedly, I found plants lacking telomerase for seven generations can lengthen telomeres when telomerase is reintroduced, but one generation is not sufficient to reestablish the telomere set point. Est1 is a non-catalytic component of the Saccharomyces cerevisiae telomerase holoenzyme. To investigate the role of Est1 in higher eukaryotes, I identified two putative Est1 homologues in Arabidopsis, AtEST1a and AtEST1b. Plants deficient in AtEST1a displayed no vegetative or reproductive defects. However, plants deficient for AtEST1b were sterile and had severe ...
TY - JOUR. T1 - Telomere length and physical performance among older people - the Helsinki Birth Cohort Study. AU - Åström, Max J.. AU - von Bonsdorff, Mikaela B.. AU - Perälä, Mia-Maria. AU - Salonen, Minna K.. AU - Rantanen, Taina. AU - Kajantie, Eero. AU - Simonen, Mika. AU - Pohjolainen, Pertti. AU - Haapanen, Markus J.. AU - Guzzardi, Maria A.. AU - Iozzo, Patricia. AU - Kautiainen, Hannu. AU - Eriksson, Johan G.. PY - 2019/10. Y1 - 2019/10. KW - 3142 Public health care science, environmental and occupational health. KW - Biomarkers. KW - Physical function. KW - Aging. KW - Epidemiology. KW - Biomarkers. KW - Physical function. KW - Aging. KW - Epidemiology. KW - MORTALITY. KW - ASSOCIATION. KW - FRAILTY. KW - BIOMARKERS. KW - DISABILITY. KW - CAPABILITY. KW - FITNESS. KW - MARKERS. KW - HEALTH. KW - BLOOD. U2 - 10.1016/j.mad.2019.111145. DO - 10.1016/j.mad.2019.111145. M3 - Article. VL - 183. JO - Mechanisms of Ageing and Development. JF - Mechanisms of Ageing and Development. SN - ...
Postdoctoral position to study telomere structure and function. A postdoctoral position is available to investigate telomere dynamics in Saccharomyces cerevisiae in the laboratory of Art Lustig at Tulane University Medical Center. We have had a long-standing fascination in telomere structure and function and are currently focusing on two broad areas: 1) The mechanisms of nucleation and inheritance of telomeric silencing (e.g. MCB 16: 2843); and 2) the mechanism of telomere size maintainence (e.g. Genes Dev. 10: 1310). Candidates should have a background in molecular biology and/or genetics. Background in yeast is preferable but not required. Interested candidates should send their c.v. either by e-mail, fax, or mail to the address listed below. Arthur J. Lustig Associate Professor Department of Biochemistry SL43 Tulane University Medical Center 1430 Tulane Avenue New Orleans, LA 70112 phone: 504-584-3688 fax: 504-584-2739 ...
Knowing that pluripotent embryonic cells are telomerase positive, we could freely draw conclusion that all of them should have similar telomeres length. However, it has been shown that the telomere length in the oocytes and blastocysts differs greatly from the telomeres in the zygote, more than it had been expected [86]. While an average oocytes telomere length has been determined as ~ 11.12 kb and a blastocysts as 12.22 kb, the average telomere length for the cleavage stage embryo is ~ 8.43 kb [87]. It is speculated that the alternative lengthening of telomeres (ALT) mechanism through chromosomal recombination in early embryo cells could yield in this discrepancy [88]. The ALT pathway has not yet been observed in human embryo cells, but it already has been shown that both mechanisms (telomerase-dependent and -independent) coexist in the same cell, which possibly could explain the differential telomeres length phenomenon in the human embryo cells [89,90]. Moreover, it has been reported that ...
The lab studies telomeres, protective elements at the ends of chromosomes that are critical for genome integrity and shorten with cell division. de Lange seeks to understand how telomeres are protected by a protein complex called shelterin, how they are replicated and maintained, and how telomere loss contributes to genome instability in cancer. The lab also studies DNA double-strand break repair with emphasis on the function of two critical DNA repair proteins, BRCA1 and 53BP1. Research in the de Lange lab focuses on human and mouse telomeres, which are made up of long arrays of double-stranded TTAGGG repeats that end in a single-stranded 3′ overhang. The lab identified a six-subunit protein complex, which they named shelterin, that specifically binds to telomeres. Using genetic approaches, de Lange and her colleagues determined the fate of telomeres lacking one or more of the six shelterin subunits. The results showed that cells lacking shelterin perceive their natural chromosome ends as ...
The human Xp/Yp telomere-junction region exhibits high levels of sequence polymorphism and linkage disequilibrium. To determine whether this is a general feature of human telomeres, we have undertaken sequence analysis at the 12q telomere and have extended the analysis at Xp/Yp. A total of 22 single-nucleotide polymorphisms (SNPs) and one 30-bp duplication were detected in the 1,870 bp adjacent to the 12q telomere. Twenty polymorphic positions were in almost complete linkage disequilibrium, creating three common diverged haplotypes accounting for 80% of 12q telomeres in the white population. A further 6% of 12q telomeres contained a 1,439-bp deletion in the DNA flanking the telomere. The remaining 13% of 12q telomeres did not amplify with the primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar distribution patterns were associated with the same haplotype in the telomere-adjacent DNA. These data suggest ...
In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P , 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescenceassociated β-galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. ...
Our lab is interested in telomere function, the regulation of telomere length and the biochemistry of telomerase. Telomeres are essential for both chromosome stability and for length maintenance. Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomere repeats onto chromosome ends. Telomerase is required for telomerase length maintenance: in the absence of telomerase, telomeres shorten progressively. To understand the telomerase, we initially focused on the well characterized Tetrahymena enzyme. We extensively characterized the functional regions of the Tetrahymena telomerase RNA. Using a reconstitution system, we mapped the essential RNA functional region. To extend this analysis to mammalian telomerase we established the secondary structure of the vertebrate telomerase RNA. We cloned and sequenced telomerase RNA genes from 35 vertebrate species and determined the secondary structure using phylogenetic comparative analysis. We identified four highly conserved domains in ...
A new study reported in the press this week looks at the relationship of exercise to expression of telomerase and telomere lengths in athletes and non-athletes. Other studies on the same topic have appeared in the last year or so. My purpose here is to review these studies in the context of some earlier studies. It is not just a simple matter of the more and the harder the exercise, the better.. The 12th theory of aging in my treatise Telomere Shortening and Damage forwards the hypothesis that longer telomere lengths are likely to be correlated with longer lifespans and that keeping ones telomeres as long as possible through expression of telomerase is vital for health and longevity. I have devoted numerous blog entries to telomeres and telomerase, including most recently Timely telomerase tidbits, Breakthrough telomere research finding, and Telomere and telomerase writings. On the other hand, it is also well established that regular exercise is also strongly supportive of ...
Telomere Binding Activity (TBA), an abundant protein from Saccharomyces cerevisiae, was identified by its ability to bind to telomeric poly(C1-3A) sequence motifs. The substrate specificity of TBA has been analyzed in order to determine whether the activity binds to a unique structure assumed by the …
(2016) Biron-Shental et al. Placenta. Objective Diabetes during pregnancy causes an intrauterine environment that influences lifetime sickness of the mother and the fetus. There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in ...
In almost all eukaryotes, the task of solving the end-replication problem and counteracting telomere erosion is assigned to the telomerase enzyme complex (Greider and Blackburn, 1985). The active telomerase holoenzyme in mammalian cells exists as a dimer and consists of the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC) and dyskerin (Cohen et al., 2007). In humans, telomerase is expressed during the early stages of embryogenesis, and its expression is subsequently repressed in most somatic cells, except the male germ line, activated lymphocytes and stem cells found in certain regenerative tissues (Wright et al., 1996). Furthermore, the vast majority of human cancer cells reactivate telomerase, and are thus capable of proliferating indefinitely (Kim et al., 1994). Regulation of telomerase is primarily exerted at the level of TERT transcription. Extensive analysis of the promoter region has uncovered many transcriptional binding sites and regulatory elements, ...
Fig. 3. NHP2 mutations result in short telomeres and reduced TERC levels. (A) Telomere length measurements in 112 healthy control subjects (open circles) are plotted against age with a line of best fit. Members of families in which NHP2 mutations are segregating are shown as gray triangles (Y139H heterozygotes), a black triangle (Y139H homozygote), gray square (V126M heterozygote), gray diamond (X154R heterozygote), black diamond (V126M/X154R, compound heterozygote), and open diamond (normal sibling). (B) Age-adjusted telomere lengths (delta tel, the difference between the observed telomere length and the length expected from the line of best fit drawn in panel a) for healthy control subjects (open circles, n = 112), NHP2 family members (as in A), and patients with dyskerin mutations (dashes, n = 67). (C) TERC levels, expressed as a TERC/ABL ratio, in healthy control individuals (open circles, n = 24), NHP2 family members (as in A), and patients with dyskerin mutations (dashes, n = 27). ...
The mechanism of telomere elongation by telomerase. In this example the telomerase enzyme is synthesizing the repeated sequence TTGGGG, which is the telomeric sequence of Tetrahymena thermophila.. The first detection of telomerase activity, in the ciliateTetrahymena thermophila, was followed by its detection in a variety of organisms including vertebrates, yeast, and plants. In the absence of telomerase activity, telomeres shorten with each cell division. Normal human somatic cells lack detectable telomerase activity, whereas telomerase is activated in germ cells, immortalized cells and the majority of primary tumors. The correlation between telomerase activity and tumor growth has spurred investigations of the possiblities to use telomerase activity as a target for anticancer drug treatments.. Our identification of much longer telomeric repeat units (16-26 bp) in several yeast species has expanded the previous range of telomeric repeat sequences to include not only more complex sequences, but ...
Mutations in the gene for telomerase reverse transcriptase (hTERT) are associated with diseases including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis and cancer. Understanding the molecular basis of these telomerase-associated diseases requires dependable quantitative measurements of telomerase enzyme activity. Furthermore, recent findings that the human POT1-TPP1 chromosome end-binding protein complex stimulates telomerase activity and processivity provide incentive for testing variant telomerases in the presence of these factors. In the present work, we compare multiple disease-associated hTERT variants reconstituted with the RNA subunit hTR in two systems (rabbit reticulocyte lysates and human cell lines) with respect to telomerase enzymatic activity, processivity and activation by telomere proteins. Surprisingly, many of the previously reported disease-associated hTERTalleles give near-normal telomerase enzyme activity. It is possible that a small deficit in telomerase activity is
In the new paper published in Nature Communications, the group of Gian Paolo Dotto describes the central role of CSL in telomere homeostasis of dermal fibroblasts with important implications for genomic instability of cancer stromal cells
See related article, pp 420-425. The discovery that critical telomere shortening initiates replicative senescence triggered a vast body of epidemiological studies exploring its implications for human aging. These studies demonstrated that telomeres-typically measured in the DNA isolated from blood cells-clearly shorten with age. On average, shorter telomeres were found in subjects with atherosclerosis and independently predicted atherosclerotic cardiovascular disease (ACVD)-associated mortality. Moreover, Mendelian randomization studies point to a causal role for shorter telomere length in ACVD, lending support to the hypothesis that the protective antitumor mechanism elicited by critical telomere attrition may act at the expense of unsuccessful cardiovascular aging.1 Yet, consensus is lacking on the mechanism underlying the presumed associations between shorter telomeres, atherosclerosis, and ACVD. This problem was addressed in the epidemiological research by Toupance et al,2 published in the ...
Telomerase activity is restricted in humans. Consequentially, telomeres shorten in most cells throughout our lives. Telomere dysfunction in vertebrates has been primarily studied in inbred mice strains with very long telomeres that fail to deplete telomeric repeats during their lifetime. It is, therefore, unclear how telomere shortening regulates tissue homeostasis in vertebrates with naturally short telomeres. Zebrafish have restricted telomerase expression and human-like telomere length. Here we show that first-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopaenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescent cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is ...
Telomerase, a ribonucleoprotein with reverse transcriptase activity, enables human cells to maintain chromosomal stability and to proliferate without limits. Various stud..
Telomerase activity is involved in telomere length maintenance. Leukocytes, unlike many human somatic tissues, have detectable telomerase activity. These cells provide a normal human cell type in which to study telomerase. We studied the regulation of telomerase activity and the telomerase RNA component as leukocytes were stimulated to enter the cell cycle. In primary human leukocytes stimulated with phytohemagglutinin, telomerase activity increased , 10-fold as naturally quiescent cells entered the cell cycle. Antibodies to the T cell receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase activity in a T cell-enriched population of cells. Rapamycin, an immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2 activation, blocked telomerase induction. Hydroxyurea, an inhibitor of S phase, did not block cdk2 kinase activity or telomerase activation. In summary, telomerase is regulated in G1 phase as normal human T cells enter the cell cycle.. ...
We sought to examine the relationship between elevated transferrin saturation (TS) and measures of health status (telomere length and patient-reported health-related quality of life) to assess whether elevated TS is associated with negative patient outcomes beyond increased risk for morbidity and mortality, using a cross-sectional analysis of the Hemochromatosis and Iron Overload Screening Study supplemented with assays for leukocyte telomere length in adults ≥25 years old (n = 669). Among individuals with elevated TS (≥45 % for women and ≥50 % for men), who also had a usual source of care, only 5.2 % reported ever being told by a doctor that they had an elevated iron condition. In a fully adjusted general linear regression model controlling for demographic characteristics as well as health conditions associated with iron overload, elevated TS versus non-elevated TS was associated with worse general health status (60.4 vs. 63.8, P , 0.05), mental health status (76.5 vs. 82.2, P , 0.0001) ...
To find an answer, the team started a long-tem study on changes in telomere length. In the Vienna Woods in Austria they regularly checked 130 nest-boxes that are occupied by free-living dormice. The researchers collected the rodents buccal mucosa for three years. Thus, they could extract the DNA and determine the relative telomere length for each dormouse individually using qPCR. With this method scientists can define the amount of target DNA compared to a reference gene of the same sample.. Elongation does not only occur, it even increases in older edible dormice. We found out that the telomeres were shortened in young animals but length significantly increased once the dormice were six years old or older. To top it all, the rate of telomere elongation also increased with increasing age of the dormice, says Franz Hoelzl.. Among the variables tested, only age significantly affected RTL in a non-linear pattern with telomere length decreasing in younger and increasing in older dormice. Hoelz ...
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Recent work has yielded considerable information concerning the structure and function of telomeres and their associated sequences in the budding yeast Saccharomyces cerevisiae. The structure and maintenance of telomeres depends not only on the RNA template and the catalytic subunit of telomerase, b …
Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics. Recently, one avenue of cancer research focuses on antisense strategy to target the oncogenes or cancer driver genes, in a sequence specific fashion to down-regulate the expression of the target gene. The protein catalytic subunit, human telomerase reverse transcriptase (hTERT) and the template RNA component (hTERC) are essential for telomerase function, thus theoretically, inhibition of telomerase activity can be achieved by interfering with either the gene expression of hTERT or the hTERC of the telomerase enzymatic complex. The present study showed that phosphorothioate antisense oligonucleotide (sASO)-nuclear localization signal (NLS) peptide conjugates targeting hTERC could inhibit telomerase activity very efficiently at 5 μM concentration but less efficiently at 1 μM ...
Objective: Studies in white people have shown that telomere length, a marker of biological ageing, is shorter in individuals with coronary artery disease (CAD). South Asian Indians have a high prevalence of CAD, especially premature CAD. We examined the association of telomere length with CAD in Indian subjects.. Design: Case-control study.. Setting: Mumbai, India.. Subjects: 238 consecutive patients (aged 29-82 years), admitted to Cumballa Hill Hospital for coronary investigations or treatment and 238 control subjects (aged 30-87 years) from the same area without any clinical evidence of CAD.. Methods: Mean leucocyte telomere length was measured using a polymerase chain reaction (PCR)-based assay and expressed as a ratio (T/S ratio) of the telomere signal to that of a control single copy gene.. Results: T/S ratio was significantly lower in CAD cases compared with controls (cases 1.21 (95% CI 1.16 to 1.26); controls 1.33 (1.28 to 1.38); p = 0.0003), equivalent to approximately 166 base pairs. ...
Fusion of critically short or damaged telomeres is associated with the genomic rearrangements that support malignant transformation. We have demonstrated the fundamental contribution of DNA ligase 4-dependent classical non-homologous end-joining to long-range inter-chromosomal telomere fusions. In contrast, localized genomic recombinations initiated by sister chromatid fusion are predominantly mediated by alternative non-homologous end-joining activity that may employ either DNA ligase 3 or DNA ligase 1. In this study, we sought to discriminate the relative involvement of these ligases in sister chromatid telomere fusion through a precise genetic dissociation of functional activity. We have resolved an essential and non-redundant role for DNA ligase 1 in the fusion of sister chromatids bearing targeted double strand DNA breaks that is entirely uncoupled from its requisite engagement in DNA replication. Importantly, this fusogenic repair occurs in cells fully proficient for non-homologous ...
The foundational understanding of the role of telomeres and telomerase in disease has been rooted in curiosity-driven science, in simple systems and model organisms (22). One major theme that emerges at the intersection between this fundamental science and disease genetics is that relatively small, subtle changes affecting telomerase abundance or function can influence telomere length and, in turn, disease risk (23). The exquisite sensitivity of telomere length to these small changes is related to the fact that telomerase is in very low abundance and its activity is tightly regulated. In yeast, mice, and humans, the number of telomere ends exceeds the number of telomerase molecules (refs. 24, 25, and reviewed in refs. 23, 26). The low levels of telomerase set up a system wherein not all telomeres are elongated during a given cell cycle even when telomerase is normally expressed (27). There are at least three additional limits on telomerase activity. The first is that the essential telomerase ...
Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal...
... most telomeres shorten, but sperm telomeres increase in length.[16] The offspring of older fathers have longer telomeres in ... Telomere length[edit]. Telomeres are repetitive genetic sequences at both ends of each chromosome that protect the structure of ... It found that telomere length was 70% heritable.[47] DNA point mutations[edit]. In contrast to oogenesis, the production of ... Since telomere length has effects on health and mortality, this may have effects on health and the rate of aging in these ...
The importance of telomeres is now clearly evident: lengthen the telomeres, lengthen the life.[1] ... However, a study of the comparative biology of mammalian telomeres indicated that telomere length correlates inversely, rather ... Telomerase is an enzyme that replenishes the worn away telomeres by adding bases to the ends and thus renewing the telomere. A ... of myonuclei contain damaged telomeres and this percentage does not increase with age.[5] Thus telomere shortening does not ...
Again, it can be presumed that a reduction in TERC results in aberrant telomere maintenance and thus shortened telomeres. Those ... the telomere, during development. Telomeres are placed by telomerase on both ends of linear chromosomes as a way to protect ... Dyskeratosis congenita is a disorder of poor telomere maintenance mainly due to a number of gene mutations that give rise to ... May 1996). "Telomere length regulation". Annu. Rev. Biochem. 65: 337-365. doi:10.1146/annurev.bi.65.070196.002005. PMID 8811183 ...
... end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres ... Telomerase reverses telomere shortening. Telomerase restores short bits of DNA known as telomeres, which are otherwise ... Cherif H, Tarry JL, Ozanne SE, Hales CN (March 2003). "Ageing and telomeres: a study into organ- and gender-specific telomere ... A comparative biology study of mammalian telomeres indicated that telomere length of some mammalian species correlates ...
Telomeres When telomeres of chromosomes shorten with continued cell divisions, the chromosome ends may also fuse, forming ... Chromosomal inversion Telomeres Cytogenetics Nuclear radiation Intellectual disorders Nussbaum, Robert; McInnes, Roderick; ... Boukamp, Petra; Popp, Susanne; Krunic, Damir (2005-11-01). "Telomere-Dependent Chromosomal Instability". Journal of ...
Telomere is a mysterious terrorist organization that is behind the attacks on The Bund. Katie Maurice A female vampire who ... It is later revealed that he is a mole for Telomere. The Eight Elite consists of the best hunters in the Earth Clan. Each ... Hysterica had a habit of referring to her slaves as "Pigs." In the anime, she worked for Telomere, but still tried to contact ... In the anime, it is heavily suggested one or all of them are controlling Telomere, a terrorist group created to kill Mina. Also ...
Telomere Cairns, John (1975). "Mutation selection and the natural history of cancer". Nature. 255 (5505): 197-200. Bibcode: ...
i.e., telomere length variation); epigenomics/epigenetics, organismal and corresponding cell specific transcriptomic regulating ...
In 1999 it was reported that telomeres, which cap the end of chromosomes, terminate in a lariat-like structure termed a T-loop ... Griffith, J. D.; Comeau, L.; Rosenfield, S.; Stansel, R. M.; Bianchi, A.; Moss, H.; De Lange, T. (1999). "Mammalian telomeres ... Greider, C. W. (1999). "Telomeres do D-loop-T-loop". Cell. 97 (4): 419-422. doi:10.1016/s0092-8674(00)80750-3. PMID 10338204. ... Maestroni L, Matmati S, Coulon S (2017). "Solving the Telomere Replication Problem". Genes. 8 (2): E55. doi:10.3390/ ...
Thus, reprogramming leads to the restoration of embryonic telomere length, and hence increases the potential number of cell ... It was found that reprogramming leads to telomere lengthening and subsequent shortening after their differentiation back into ... West, M. D.; Vaziri, H (2010). "Back to immortality: The restoration of embryonic telomere length during induced pluripotency ... Marión, R. M.; Blasco, M. A. (2010). "Telomere rejuvenation during nuclear reprogramming". Current Opinion in Genetics & ...
Author of The Telomere (1995). Professor Thomas Burton Loram Kirkwood CBE (1951-) Dr James Brown (1975-)Elected to membership ( ...
The study was halted early, after telomere attrition was reduced in all 12 patients who could be evaluated. 12 of 27 patients ... A 2016 phase I/II prospective study orally administered 800 mg per day to 27 patients with telomere diseases. The primary ... "Danazol Treatment for Telomere Diseases". N. Engl. J. Med. 374 (20): 1922-31. doi:10.1056/NEJMoa1515319. PMC 4968696. PMID ... efficacy endpoint was a 20% reduction in the annual rate of telomere attrition measured. Toxic effects formed the primary ...
Telomeres may extend from both ends of the chromosome, their shape is similar to letter "i" during anaphase. For example, the ... Telomere Chromatid Diploid Monopolin Alberts, Bruce; Bray, Dennis; Hopkin, Karen; Johnson, Alexander; Lewis, Julian; Raff, ...
In plants, the telomere sequence is conserved, which implies that this strategy can be utilized to successfully construct ... Yu, W.; Lamb, J. C.; Han, F.; Birchler, J. A. (2006). "Telomere-mediated chromosomal truncation in maize". Proceedings of the ... A minichromosome is a small chromatin-like structure resembling a chromosome and consisting of centromeres, telomeres and ... The minimum constituent parts of a chromosome (centromere, telomeres, and DNA replication sequences) are assembled by using ...
Another example related to aging is the Telomere theory. Telomere theory proposes that telomeres shorten with repeated cell ... However, there is still the question whether telomere length causes these diseases or if the diseases cause shortened telomeres ... Telomere shortening is common in somatic cells. However, germ line and stem cells prevent the end replication problem with the ... The trade-off exists as the cell benefits from telomerase which prevents permanent growth arrest but telomere shortening is ...
Her research focuses on the role of telomeres in disease. Armanios graduated from the Ohio State University with a doctorate in ... Armanios is a Professor of Oncology at Johns Hopkins University School of Medicine and the Clinical Director of the Telomere ...
Telomere loss can be lethal for many cells, but in the few that are able to restore the expression of telomerase can bring ... Telomeres - which are a protective 'cap' at the end of DNA molecules - normally shorten in each replication cycle. In certain ... However, telomere degeneration can also induce tumorigenesis in other cells. The key difference is the presence of a functional ... Telomere shortening and p53 expression is a key mechanism to prevent uncontrolled replication and tumor development because ...
In general, TERRA has been shown to be most abundant in cells with long telomeres, while cells with short telomeres express ... Generally speaking, cells with long telomeres exhibit greater TERRA expression while short telomeres have relatively lower ... telomerase activity is known to be at its greatest when telomeres are short and at its lowest activity when telomeres are long ... specifically in cells with long telomeres. This inhibitive effect seems to function in a telomere length-dependent manner; that ...
"Single-Strand DNA-Binding Protein SSB1 Facilitates TERT Recruitment to Telomeres and Maintains Telomere G-Overhangs". Cancer ... Is involved with maintaining telomere length. DNA-binding protein Replication protein A Comparison of nucleic acid simulation ...
The book hones in on many of the effects that poor health can have on telomeres and telomerase activity. Since telomeres ... Blackburn, co-founded the company Telomere Health which offers telomere length testing to the public, but later severed ties ... telomere testing, plus cautions and advice. While studying telomeres and the replenishing enzyme, telomerase, Blackburn ... "How maintaining your telomeres can help you age healthily". Retrieved 14 December 2018. "How to beat the march of time". The ...
The shrinking of telomeres occurs in somatic cells where telomerase, the enzyme in control of telomere lengthening, is not ... Another component of aging is the gradual shortening of telomeres located at the end of chromosomes. Telomeres are repetitive ... This increase in non-coding RNA transcription aided telomere stability, making the exercise group's telomeres less likely to be ... However, it has been seen that telomeres can transcribe non-coding RNA, or functional RNAs that do not get translated into ...
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme ... Telomerase are found specifically to target shorter telomere over longer telomere, due to various regulatory mechanisms inside ... Although cells with long telomeres did not experience apoptosis, they developed mortal characteristics and underwent telomere ... It elongates the telomeres of stem cells, which, as a consequence, increases the lifespan of the stem cells by allowing for ...
... but also for maintaining telomere length and stability. Thus, WRN helicase is important for preventing catastrophic telomere ... In addition to telomere dysfunction, over-expression of oncogenes and oxidation can induce this type of response. High stress ... While evidence shows that telomere dysfunction is consistent with the premature aging in WS, it has yet to be determined if it ... This event can be counteracted by telomerase, an enzyme that extends the ends of the chromosomes by copying the telomeres and ...
TRF1 along with TRF2 normally prevents telomerase from adding more telomere units to telomeres. But when telomere lengthening ... When telomeres are to be lengthened, TPP1 is a central factor in recruiting telomerase to telomeres. TPP1 promotes telomerase ... Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) ... Both TRF1 and TRF2 recruit the other four subunits to the telomere. Both TRF1 and TRF2 participate in telomere replication as ...
Ty5 is used as a model system by which to understand the biology of the telomere and heterochromatin. The Ty5 retrotransposon ... Pryde FE, Louis EJ (November 1997). "Saccharomyces cerevisiae telomeres. A review". Biochemistry Mosc. 62 (11): 1232-41. PMID ... which interact with specific cis DNA sequences at the telomeres, rDNA and HM loci. These proteins, including Rap1p and the ... "The Saccharomyces Ty5 retrotransposon family is associated with origins of DNA replication at the telomeres and the silent ...
S. pombe has a shelterin-like telomere complex while S. cerevisiae does not. S. cerevisiae is in the G1 phase of the cell cycle ... Price CM, Boltz KA, Chaiken MF, Stewart JA, Beilstein MA, Shippen DE (August 2010). "Evolution of CST function in telomere ... telomere function, gene splicing, and many other cellular processes. S. pombe's genome was fully sequenced in 2002, the sixth ...
1992). "Telomere length predicts replicative capacity of human fibroblasts". Proc. Natl. Acad. Sci. U.S.A. 89 (21): 10114-10118 ... Frenck RW Jr, Blackburn EH, Shannon KM (1998). "The rate of telomere sequence loss in human leukocytes varies with age". Proc. ... 1996). "Accelerated telomere shortening in ataxia telangiectasia". Nat. Genet. 13 (3): 350-353. doi:10.1038/ng0796-350. PMID ... 1990). "Telomere reduction in human colorectal carcinoma and with ageing". Nature. 346 (6287): 866-868. Bibcode:1990Natur.346.. ...
Zhang H, Cohen SN (Dec 2004). "Smurf2 up-regulation activates telomere-dependent senescence". Genes & Development. 18 (24): ...
They elucidated how telomere shortening is counteracted by the telomerase enzyme that renders cancer cells immortal. The lab ... The Lingner Lab studies of the structure, function and maintenance of telomeres, the nucleoprotein complexes at the ends of ... Teixeira, M.Teresa; Arneric, Milica; Sperisen, Peter; Lingner, Joachim (2004). "Telomere Length Homeostasis is Achieved via a ... Teixeira, M.Teresa; Arneric, Milica; Sperisen, Peter; Lingner, Joachim (April 2004). "Telomere Length Homeostasis Is Achieved ...
One hypothesis for the detrimental results of aging is associated with the loss of telomeres, the end segments of chromosomes ... Telomere loss has also been associated with decreased mitochondrial function. Deficiency of telomerase reverse transcriptase ( ... February 2011). "Telomere dysfunction induces metabolic and mitochondrial compromise". Nature. 470 (7334): 359-65. doi:10.1038/ ... Therefore, the loss of telomeres and TERT that comes with aging has been associated with impaired mitochondrial biogenesis. ...
... and terminal restriction fragment analysis have traditionally been regarded as the gold standard for measuring telomere length ... Approaches and challenges in studies of telomere length. When a research study wants to include telomere length in the analysis ... The length of the shortest telomere represents a much better indicator of cellular aging than the average telomere length, ... yielding a telomere/gene ration as a measure of telomere length. Still, even when performed by experts, there can be a ...
This is the reason why adequate telomere structure (including the presence of telomere-binding proteins) remains pivotal for ... The telomeres are special structures on the chromosome ends that are essential for providing protection from enzymatic end- ... Roles of telomeres and telomerase. The properties of the eukaryotic telomeres are usually identified as the "capping function ... General telomere structure. Telomeres are composed of a DNA component characterized by noncoding repetitive sequences rich in ...
Telomeres become shorter every time a cell divides. Once they are too short, telomeres send a signal for the cell to stop ... New Insight into Telomere Regulation New Insight into Telomere Regulation * Prenatal Lead Exposure Linked with Decreased ... oxoG lesion arises in telomeres dictates whether telomerase is inhibited or stimulated and thus determines whether the telomere ... Research, funded in part by NIEHS, has uncovered new details about the regulation of telomeres. These repeated DNA sequences ...
... and protection of telomeres 1 (POT1) - which are essential for telomere protection and for regulating telomere elongation. The ... a , Simplified schema of the haematopoiesis hierarchy with intact telomere length (left panel) and in the presence of telomere ... The telomere syndromes.. Armanios M1, Blackburn EH.. Author information. 1. Department of Oncology, Sidney Kimmel Comprehensive ... At every age, telomere length displays a normal distribution that is defined by the percentile lines labelled on the right. ...
The telomere is a nucleoprotein structure comprising the terminal section of a eukaryotic chromosome. It has a specialized ...
... known as telomeres, protect chromosome ends from nucleolytic degradation and DNA repair activities. Conventional DNA ... Telomere Length Short Telomere Cajal Body Telomere Elongation Nonextendible State These keywords were added by machine and not ... Correct telomere length setting is crucial for long-term survival. The telomere length reserve must be sufficient to avoid ... In vivo analysis of telomere elongation kinetics shows that telomerase does not act on every telomere in each cell cycle but ...
... although telomere shortening may play a role in limiting cellular life span, there is no evidence that telomere shortening ... long-lived species often have shorter telomeres than do short-lived species, indicating that telomere length probably does not ... 56Kakuo S, Asaoka K, Ide T. Human is a unique species among primates in terms of telomere length. Biochem Biophys Res Commun. ... Telomeres shorten during ageing of human fibroblasts. Nature 1990;345:458-460. 54Vaziri H, Dragowska W, Allsopp RC, Thomas TE, ...
The question remains whether Dollys short telomeres were an exception or a general fact, which would differ from the telomeres ... inherited shortened telomeres from her cell donor and that her telomeres were further shortened by the brief culture of donor ... This observation was challenged by a recent report9 that showed calves cloned from fetal cells have longer telomeres than their ... The question remains whether Dollys short telomeres were an exception or a general fact, which would differ from the telomeres ...
... rapid advances in technology have equipped us with a variety of tools and platforms to ask fundamental questions of telomere ... Cancer progression Cell growth Chromatin Genomics Model systems Protein interaction networks Proteomics Telomere DNA Telomere ... Telomeres and Telomerase: Methods and Protocols, Second Edition builds upon the telomerase assays featured in the popular first ... Authoritative and practical, Telomeres and Telomerase: Methods and Protocols, Second Edition serves as an ideal, up-to-date ...
Although leukocyte telomeres shorten with age, sperm telomeres lengthen with age. Shorter telomeres are theorized to impose ... These function in both telomere maintenance and capping. Telomeres form large loop structures called telomere loops, or T-loops ... At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere ... Telomere shortening is associated with aging, mortality and aging-related diseases. Normal aging is associated with telomere ...
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Telomere resolvase, also known as protelomerase, is an enzyme found in bacteria which contain linear plasmids. In order to ... Telomere resolvase then cuts the structure and reforms the hairpin turns, forming two new, identical linear plasmids. Shi, Ke; ... Huang, Wai Mun; Aihara, Hideki (2013). "An enzyme-catalyzed multistep DNA refolding mechanism in hairpin telomere formation". ...
Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. ...
... and telomere length implies that stress preceded telomere shortening, because telomere length cannot have influenced the number ... A) Average telomere length and SE are shown. The high-stress group had shorter telomeres even after controlling for age and BMI ... Therefore, in translating telomere shortening to years of aging, we based our estimates on studies averaging telomere ... Telomeres are DNA-protein complexes that cap chromosomal ends, promoting chromosomal stability. When cells divide, the telomere ...
In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with ... To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length ... Inheritance of telomere length in a bird.. Horn T1, Robertson BC, Will M, Eason DK, Elliott GP, Gemmell NJ. ... with many correlations reported between telomere length and age-related diseases, cancer and death. While telomere length is ...
... those whose donor white blood cells had longer telomeres had higher survival rates five-years after transplant ... Donor telomere length and survival after hematopoietic cell transplantation in patients with severe aplastic anemia. * ... Telomere length has been implicated in the development of several cancers, as well as other health conditions. This study was ... Telomeres are complex structures on the ends of chromosomes that help maintain chromosome integrity. They shorten naturally as ...
... collectively called a telomere. With each cell division, telomeres are copied and reassembled through a process called telomere ... I will use purified proteins to study telomere replication in a test tube. This novel approach will allow me to use biochemical ... My work will provide fundamental molecular insights into the biology of telomeres, which will help us better understand human ... Understanding the mechanism of telomere replication. Sir Henry Dale Fellowships Year of award: 2019 ...
There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in ... There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in ... Telomere homeostasis in placentas from pregnancies with uncontrolled diabetes. *Biron-Shental T ... TERC gene copy number and telomere capture were evaluated by FISH. Results Telomerase expression was significantly lower in the ...
Cells age if the telomeres are shortened, but when "telomerase activity is high, telomere length is maintained, and cellular ... Americans Win Nobel for Telomere Discovery. - Three American scientists, whose research held the key to unlocking chromosome ... Blackburn and Szostak discovered that the solution to chromosome replication was contained in telomeres, the structure at the ... Greider was a graduate student when she and and Blackburn identified telomerase, the enzyme that makes telomere DNA. ...
Telomere Dynamics Telomere overhang generation processes and the end-replication problem. Telomeres are composed of TTAGGG ... From previous studies, we found that telomere overhang generation processes may be important in determining telomere shortening ... We found that the telomere lagging strand has an overhang of ~110 nt and the leading strand has an overhang of ~30 nt. These ... If that were correct, the rate of telomere shortening would only be around 8-10 bp per cell division (RNA primer size ÷ 2 = (16 ...
Telomeres are tail-like chains of DNA at the ends of chromosomes that protect chromosomes during cell division. In many cell ... Longer telomeres accumulate more probes and fluoresce more brightly. The technique can be used with a microscope and electronic ... Researchers find shortened telomeres linked to dysfunction in Duchenne muscular dystrophy New method from Penn researchers ... "We found that in boys with DMD, the telomeres are so short that the muscle stem cells are probably exhausted," said the studys ...
... A telomere is a region of highly repetitive DNA at the end of a linear chromosome that functions as a disposable ... Telomere sequences. Some known telomere sequences Group Organism Telomeric repeat (5 to 3 toward the end) ... The telomere length varies in cloned animals. Sometimes the clones end up with shorter telomeres since the D.N.A. has already ... Telomere shortening. "Telomeres" shorten because of the end replication problem that is exhibited during DNA replication in ...
Find telomere Stock Images in HD and millions of other royalty-free stock photos, illustrations, and vectors in the ... Telomere stock photos. 568 Telomere stock photos, vectors, and illustrations are available royalty-free. See telomere stock ... Telomeres DNA and telomere length medical concept on the end caps of a chromosome as a symbol for aging and genetic protection ... Telomeres length loss with DNA and shortening telomere medical concept as a tree with falling leaves on the end caps of a ...
Shop for Enzymedica Telomere Plus at Ralphs. Find quality products to add to your Shopping List or order online for Delivery or ... Telomerase is a naturally occurring enzyme that lengthens telomeres and protects them from shortening. Telomere Plus™ has been ... Telomeres are the protective tips at ht ends of chromosomes that protect our DNA. When the cell divides, the tips shorten. Over ... Cellular aging is the process by which a ell becomes old and dies due in large part to the shortening of its telomeres. ...
telomeres Archive antiaging100 years ago the world absolute poverty rate was as bad as the poorest country today. No Comments ...
This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can ... Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at ... In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity ... Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. ...
Telomere and Telomerase. The safety and scientific validity of this study is the responsibility of the study sponsor and ...
Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also ... Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. ... This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and ... The pervasive role of magnesium in telomere homeostasis is also highlighted. ...
This process shortens the telomeres or scalar antenna on the DNA which as they get shorter limits the ability to grow new cells ... We use the Viopulsar for activating the amazing Telomerase enzyme and the Telomeres. Facial: 2-3 sessions weekly Set the SWL on ... scientists have recently discovered an enzyme called the Telomerase enzyme which increases the length of the telomere thereby ... and the violet laser spectrum optimizes and enhances this quantum rejuvenation effect of activating Telomerase and the Telomere ...
The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic ... Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and ... thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis ... Telomere dysfunction induces metabolic and mitochondrial compromise Nature. 2011 Feb 17;470(7334):359-65. doi: 10.1038/ ...
  • therefore, measuring telomere length represents an important approach to study the stressed and aging cell, as well as to gain insights into the different mechanisms. (news-medical.net)
  • Southern blotting and terminal restriction fragment analysis have traditionally been regarded as the gold standard for measuring telomere length. (news-medical.net)
  • The problem with trying to identify what is happening in DMD muscle stem cells is that we've lacked sufficient tools for measuring telomere length in these stem cells," Mourkioti said. (eurekalert.org)
  • The telomeres at the end of human chromosomes are responsible for safeguarding DNA termini while chromosome replication is taking place. (news-medical.net)
  • Other measurement methods use cytometry hybridization techniques, which are designed to measure the shortest telomeres, as well as telomeres from specific chromosomes. (news-medical.net)
  • The physical ends of chromosomes, known as telomeres, protect chromosome ends from nucleolytic degradation and DNA repair activities. (springer.com)
  • Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. (wikipedia.org)
  • Telomeres are non-coding, repetitive sequences located at the termini of linear chromosomes to act as buffers for those coding sequences further behind. (wikipedia.org)
  • Most prokaryotes, relying on circular chromosomes, accordingly do not possess telomeres. (wikipedia.org)
  • A small fraction of bacterial chromosomes (such as those in Streptomyces, Agrobacterium, and Borrelia), however, are linear and possess telomeres, which are very different from those of the eukaryotic chromosomes in structure and function. (wikipedia.org)
  • The known structures of bacterial telomeres take the form of proteins bound to the ends of linear chromosomes, or hairpin loops of single-stranded DNA at the ends of the linear chromosomes. (wikipedia.org)
  • Telomeres, the repeated sequence found at the ends of chromosomes, shorten in many normal human cells with increased cell divisions. (scientificamerican.com)
  • Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. (pnas.org)
  • To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length in a bird species, the kakapo (Strigops habroptilus), in which females are the heterogametic sex (ZW) and males are the homogametic (ZZ) sex. (nih.gov)
  • Telomeres are complex structures on the ends of chromosomes that help maintain chromosome integrity. (cancer.gov)
  • The genetic material in our cells is packaged into linear chromosomes, which are protected at each end by a special cap made up of DNA and a collection of proteins, collectively called a telomere. (wellcome.ac.uk)
  • With each cell division, telomeres are copied and reassembled through a process called telomere replication, which ensures chromosomes stay capped from one generation to the next. (wellcome.ac.uk)
  • Blackburn and Szostak discovered that the solution to chromosome replication was contained in telomeres, the structure at the end of the chromosome, which protect chromosomes from degradation during cell divisions. (medpagetoday.com)
  • Telomeres are composed of TTAGGG repeated sequences located at the end of chromosomes. (utsouthwestern.edu)
  • Telomeres are tail-like chains of DNA at the ends of chromosomes that protect chromosomes during cell division. (eurekalert.org)
  • Telomeres are the protective tips at ht ends of chromosomes that protect our DNA. (ralphs.com)
  • Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. (mdpi.com)
  • Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. (mdpi.com)
  • Telomeres are the protective ends of linear chromosomes. (genetics.org)
  • THE work of H. J. Muller and Barbara McClintock defined telomeres as the protective ends of linear chromosomes. (genetics.org)
  • The ends of most eukaryotic linear chromosomes terminate in telomeric DNA, repeats of 5-25 bp that vary in sequence among species and end in a 3′ single-stranded overhang ( W ellinger and S en 1997 ). (genetics.org)
  • Telomeres are repetitive sequences that protect the ends of chromosomes, but they shrink as cells divide and age. (sciencemag.org)
  • WASHINGTON, DC - June 27, 2013 - Researchers from the Japanese Foundation for Cancer Research in Tokyo have discovered that forced elongation of telomeres (extensions on the end of chromosomes) promotes the differentiation of cancer cells, probably reducing malignancy, which is strongly associated with a loss of cell differentiation. (asm.org)
  • Telomeres are protective extensions on the ends of chromosomes, which shorten as cells age, like an hourglass running down. (asm.org)
  • Without telomeres chromosomes would progressively lose genetic information as cells divide and replicate. (asm.org)
  • Telomeres (strings of DNA that protect chromosomes) shorten due to stress. (sharecare.com)
  • Telomeres are small strips of DNA that cover the ends of chromosomes - they are similar to the plastic coverings on shoelace tips. (mdtmag.com)
  • Telomeres are unique complexes of protein and DNA that cap the ends of chromosomes and protect them from abnormal fusion events. (asbmb.org)
  • Telomere maintenance is also possible by other mechanisms, such as the alternative pathway (ALT), which uses recombination between chromosomes to maintain telomere length. (the-scientist.com)
  • In ALT, telomeres are not newly elongated, but rather transferred from one chromosome to another, resulting in some daughter cells whose chromosomes have shorter telomeres and others with longer telomeres. (the-scientist.com)
  • Telomeres are found on the end of chromosomes and these aide the process of replication of cells, protecting them from deteriorating. (privatehealth.co.uk)
  • Eukaryotic chromosomes terminate in telomeres, nucleoprotein complexes thought to mask chromosome ends from the machinery that detects and repairs damaged deoxyribonucleic acid (DNA). (els.net)
  • The human telomere is a simple repeating sequence of six bases, TTAGGG, located at the ends of chromosomes. (wiley.com)
  • 2 It is thought that telomeres have multiple roles, including protection against degeneration, reconstruction, fusion and loss, 3 as well as contributing to pairing of homologous chromosomes. (wiley.com)
  • Telomeres are found on the tips of chromosomes and protect the chromosomes from damage, like the plastic tip on the end of a shoelace. (mdanderson.org)
  • Telomeres are protective segments of DNA at the ends of chromosomes, and telomerase is the protein responsible for maintaining the telomere-forming DNA sequences. (nih.gov)
  • Short telomeres - the protective caps on the ends of chromosomes - have been previously linked to increased risk of death from heart disease. (scienceblog.com)
  • Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. (hindawi.com)
  • PHILADELPHIA - (Dec. 11, 2014) - A team of scientists, led by researchers at The Wistar Institute, has found that an infection with herpes simplex virus 1 (HSV-1) causes rearrangements in telomeres, small stretches of DNA that serve as protective ends to chromosomes. (eurekalert.org)
  • Telomeres are often compared to the clear tips of shoelaces because they protect the end of chromosomes - the keepers of our vital genetic information - and prevent them from fraying and breaking, thus preserving their ability to pass on necessary genetic information. (eurekalert.org)
  • Among the viruses Lieberman and his lab have decided to study is HSV-1, a particularly aggressive virus that replicates in the nucleus of a healthy cell where chromosomes and their telomeres reside. (eurekalert.org)
  • Telomeres sit on the ends of chromosomes to protect them from damage. (popsci.com)
  • The caps of DNA at the end of our chromosomes known as telomeres are a crucial part of our biology. (rdmag.com)
  • Telomeres are the protective end caps on the ends of chromosomes, they help to keep the chromosomes from fraying or sticking together, but each time a cell a cell reproduces the telomeres gradually shorten until they become too short to function properly, and once no longer functional the cell becomes inactive or senescent. (worldhealth.net)
  • Telomeres are made of the same sequences of nucleotides that repeat over and over again, this is to cap of the chromosomes to prevent key genetic material from being lost in the division process as when one of the telomere sequences get lost in division no harm is done. (worldhealth.net)
  • Telomere, the nucleoprotein structure at the end of eukaryotic linear chromosomes is indispensable for maintaining the genome stability. (scirp.org)
  • Telomeres are chromatin structures that cap and protect the end of chromosomes. (scirp.org)
  • The end-to-end fusion of chromosomes due to gradual telomere shortening may lead to the formation of dicentric chromosomes, which mark a potential threat to cellular viability. (scirp.org)
  • Telomeres are the protein-DNA structures at the ends of eukaryotic chromosomes. (sciencemag.org)
  • Telomeres are highly conserved tandem repeats of DNA at the ends of eukaryotic chromosomes, which play an important role in genome stability and replication [ 4 ]. (royalsocietypublishing.org)
  • Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. (labspaces.net)
  • Telomeres are long, repetitive DNA sequences at the ends of chromosomes that serve a protective function analogous to that of the plastic tips on shoelaces. (labspaces.net)
  • Sugiyama and his colleagues overcame these issues by using a synthetic pyrrole-imidazole polyamide (PIP) probe that can precisely deliver a fluorescent compound to telomeres on the tips of chromosomes. (labmanager.com)
  • The ends of chromosomes are protected by specific DNA sequences called telomeres, visualized here in red. (ucsf.edu)
  • Researchers at the Institute of Molecular Biology (IMB) and at the Faculty of Biology at Johannes Gutenberg University Mainz (JGU) have further uncovered the secrets of telomeres, i.e., the caps that protect the ends of our chromosomes. (uni-mainz.de)
  • Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from unravelling. (uni-mainz.de)
  • however, telomeres and TERRA are found across all organisms with linear chromosomes. (uni-mainz.de)
  • Telomeres specialized structures found at the ends of chromosomes are essential for maintaining the integrity of chromosomes and their faithful duplication during cell division. (cshlpress.com)
  • But telomeres, structures on the ends of chromosomes, might be an alternative way to do this. (fiercebiotech.com)
  • But the Indiana University side of the research, according to the story, wants to develop blood and tissue tests that would screen for short telomeres leading to the condition known as telomere fusion--in which chromosomes improperly join together. (fiercebiotech.com)
  • While high school biology has hammered in the all too familiar double-helix shape of DNA, with chromosomes it may be easier to visualize them as a pair of shoelaces, since its telomeres are the genetic equivalent of laces' plastic caps that keep them from fraying apart at the tips. (cityofhope.org)
  • Telomeres help maintain chromosomes' integrity during replication and protein production, but a few variations in the TERT gene can causes damaging changes that lead to cancer, City of Hope researchers found. (cityofhope.org)
  • Likewise, telomeres act as protective caps at the ends of chromosomes by maintaining their integrity. (cityofhope.org)
  • Summary Telomeres are the nucleoprotein structures at the ends of linear chromosomes and maintain the genomic integrity through multiple cell divisions. (biomedsearch.com)
  • Telomeres are repetitive DNA structures that, together with the shelterin and the CST complex, protect the ends of chromosomes. (rcsb.org)
  • Human telomeres form the terminal structures of human chromosomes and play a pivotal role in the maintenance of genomic integrity and function. (fightaging.org)
  • Today, PLoS ONE published two separate studies investigating how anxiety and work-related exhaustion are correlated to the length of our telomeres, the protective caps on our chromosomes that help make sure our dividing cells have all the genetic material they need for long, healthy lives. (plos.org)
  • Telomeres are the portions at the ends of our chromosomes, the packaged-up version of all of our DNA, which are critical for proper cell functioning. (plos.org)
  • It's thought that some of the issues associated with aging and some cancers may be caused by telomere shortening, which can lead to dysfunctional cells with incomplete chromosomes that die or go rogue. (plos.org)
  • This observation was challenged by a recent report 9 that showed calves cloned from fetal cells have longer telomeres than their age-matched controls. (nature.com)
  • P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. (pnas.org)
  • In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with females having longer telomeres than males. (nih.gov)
  • A new NCI study has found that, among patients with severe aplastic anemia (SAA) who received a hematopoietic cell transplant (HCT) from an unrelated donor, those whose donor white blood cells had longer telomeres had higher survival rates five-years after transplantation than those whose donor white blood cells had shorter telomeres. (cancer.gov)
  • They found that patients whose donor white blood cells had longer telomeres had better survival than those whose donor cells had shorter telomeres. (cancer.gov)
  • Longer telomeres accumulate more probes and fluoresce more brightly. (eurekalert.org)
  • They were surprised, however, to find a group with longer telomeres. (mdtmag.com)
  • The other may be a distinct subgroup of patients with longer telomeres. (mdtmag.com)
  • It was suggested that when telomeres were found to be longer in any specific organ in a given individual, then the other organs in that individual would also have longer telomeres. (wiley.com)
  • Certain cancers are much more likely in people with longer telomeres, while other tumors' risk factors are greatly increased by the presence of shorter telomeres, said Jian-Min Yuan, the lead author. (rdmag.com)
  • Studies in adults have similarly found that women on average have significantly longer telomeres than men, but it has been hypothesized that longer telomeres in women may be due to hormonal factors or psychosocial factors which result in longer lives for women. (parentsguidecordblood.org)
  • Ours is the first study to find that females have longer telomeres at birth. (parentsguidecordblood.org)
  • The CST complex has three components - conserved telomere protection component 1 (CTC1), suppressor of cdc thirteen 1 (STN1) and telomeric pathway with STN1 (TEN1) - which are thought to function in part in telomere lagging-strand synthesis. (nih.gov)
  • Ancelin K, Brunori M, Bauwens S, Koering CE, Brun C, Ricoul M, Pommier JP, Sabatier L, Gilson E (2002) Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2. (springer.com)
  • I am seeking additional qualified postdoctoral researchers to study one of two ongoing projects: a) the role of the telomere-binding protein RAP1 in telomere size control and telomeric silencing (see Lustig et al. (bio.net)
  • Telomerase, a cellular enzyme, adds the necessary telomeric DNA (T 2 AG 3 repeats) onto the 3′ ends of the telomere ( 5 ). (pnas.org)
  • We have had a long-standing fascination in telomere structure and function and are currently focusing on two broad areas: 1) The mechanisms of nucleation and inheritance of telomeric silencing (e.g. (bio.net)
  • Furthermore, we found that neither telomere repeat length nor telomeric silencing correlated with chromosomal capping efficiency. (genetics.org)
  • The telomeric DNA sequences are synthesized by telomerase ( G reider and B lackburn 1987 ), a protein-RNA complex, and the DNA repeats are bound by telomere-specific binding proteins that, with other proteins, form a telomeric complex (reviewed in B lackburn and G reider 1995 ). (genetics.org)
  • Telomerase, a ribonucleoprotein, synthesizes telomeric DNA (telomeres) during replication. (asbmb.org)
  • Telomeric DNA is coated by a group of proteins, collectively termed shelterin, which serves to protect telomere structure. (the-scientist.com)
  • Proteins associated with the telomeric DNA sequence at chromosome ends execute and regulate the maintenance and protection functions of telomeres. (els.net)
  • 5 Telomeric repeats of DNA sequences at chromosome ends are shortened by 33-120 bp with each cell division in human fibroblasts 6 and lymphocytes 7 in vitro , but the question of telomere shortening with aging in many other cell types, and human tissues and organs in vivo remains unclear. (wiley.com)
  • Telomere shortening is mitigated in stem and cancer cells through the de novo addition of telomeric repeats by telomerase. (rcsb.org)
  • When telomeric DNA is buried within POT1, telomerase cannot access the DNA to elongate the telomere. (fightaging.org)
  • Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. (sciencemag.org)
  • Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA. (sciencemag.org)
  • Retroviral-mediated overexpression of TRF2 in primary human IMR90 fibroblasts ( 19 ) resulted in accelerated telomere shortening ( Fig. 1 , A and B). Although IMR90 cells normally lose telomeric DNA at a rate of 99 to 112 bp per end per PD, TRF2 accelerated telomere attrition by 50 to 80%, from 165 to 181 bp per end per PD ( Fig. 1 B) ( Table 1 ). (sciencemag.org)
  • In contrast to the results of overexpression of TRF2, overexpression of several forms of TRF1, a related telomeric DNA binding protein, did not affect telomere shortening, even though each of these proteins was expressed at high levels and showed the expected subnuclear localization ( Fig. 1 , A and B) ( 19 ). (sciencemag.org)
  • This is the reason why adequate telomere structure (including the presence of telomere-binding proteins) remains pivotal for avoiding cellular dysfunction. (news-medical.net)
  • Some of these proteins (most notably TIN2, TRF1, TRF2, TPP1, and POT1) are found in telomeres at any time, even though there is a highly dynamic exchange between proteins that are telomere-bound and unbound. (news-medical.net)
  • Shelterin complex components are made up of six component proteins - telomere repeat-binding factor 1 (TRF1), TRF2, repressor/activator protein 1 (RAP1), TRF1-interacting nuclear protein 2 (TIN2), TIN2-interacting protein 1 (TPP1) and protection of telomeres 1 (POT1) - which are essential for telomere protection and for regulating telomere elongation. (nih.gov)
  • Presumably through mediating formation of alternative telomere structures, telomere-binding proteins regulate telomerase activity in cis to favor preferential elongation of the shortest telomeres. (springer.com)
  • Telomeres and Telomerase: Methods and Protocols, Second Edition builds upon the telomerase assays featured in the popular first edition to encompass many different assays that allow investigators to query the function of telomere proteins and the responses of the telomere DNA, including detailed examinations of biochemical, molecular, and proteomic approaches. (springer.com)
  • I will use purified proteins to study telomere replication in a test tube. (wellcome.ac.uk)
  • In the study, the forced elongation of cancer cells' telomeres suppressed a number of genes and proteins that appear to be involved in tumor malignancy, according to the report. (asm.org)
  • One protein, SLX4, forms a complex involved in DNA repair that includes proteins recently described in telomere regulation. (qiagen.com)
  • However, many of the proteins that are known to be associated with telomeres have unknown functions. (qiagen.com)
  • Proteins associated with human telomeres. (els.net)
  • Purified and recombinant proteins TPC2 and TPC3 and recombinant or synthetic oligonucleotides corresponding to those proteins or fragments thereof can be used to detect regulators of telomere length and telomerase activity in mammalian cells and for a variety of related diagnostic and therapeutic pu. (google.com)
  • In an important embodiment, the invention provides oligonucleotide probes and primers, polynucleotide plasmids, peptides, proteins, antibodies, and enzymes relating to genes and gene products that regulate telomere length and telomerase activity in mammalian cells. (google.com)
  • This is followed by the virus degrading a telomere protein called TPP1 - part of a complex of proteins responsible for protection called "telomere sheltering" - which results in the loss of the telomere repeat DNA signal. (eurekalert.org)
  • Telomerase, the ribonucleoprotein complex, and its accessory proteins are required to maintain the telomere sequence. (scirp.org)
  • In mammals, telomeres comprise of thousands of tandem repeats of oligonucleotide sequence TTAGGG, associated with various specific proteins. (scirp.org)
  • Further, the chromosome is no longer able to bind shelterin or associated proteins, and thus telomere uncapping occurs. (scirp.org)
  • These findings have implications for understanding the molecular mechanisms of telomere-associated proteins and enzymes involved in the unfolding reaction, as well as for rational design of anti-cancer drugs, Stone said. (labspaces.net)
  • Chromosome ends are constantly at risk of degradation and fusion, so they are protected by structures called telomeres, which are made of long repeating DNA sequences and bound proteins,' says iCeMS chemical biologist Hiroshi Sugiyama, who led the study. (labmanager.com)
  • Their joint work led them to realize that TERRA actually accumulates at all telomeres, but at long telomeres it is rapidly removed with the help of proteins Rat1 and RNase H2. (uni-mainz.de)
  • These proteins bind preferentially to the long telomeres and ensure that TERRA is removed, but they are not present at the critically short telomeres, which means that TERRA remains for a longer time. (uni-mainz.de)
  • But as genes work at replicating themselves or producing proteins, the telomeres get worn down, and the cell can breakdown. (cityofhope.org)
  • Telomere repeats are lost with each round of cell replication by a plethora of different mechanisms, and most somatic cells express insufficient telomerase to compensate for the loss of telomere repeats. (news-medical.net)
  • Conventional DNA replication enzymes lack the ability to fully replicate telomere ends. (springer.com)
  • We focused this review on factors whose functions are well integrated into telomere replication and length homeostasis in S . cerevisiae or human cells. (springer.com)
  • Adams AK, Holm C (1996) Specific DNA replication mutations affect telomere length in Saccharomyces cerevisiae. (springer.com)
  • When cells divide, the telomere is not fully replicated because of limitations of the DNA polymerases in completing the replication of the ends of the linear molecules, leading to telomere shortening with every replication ( 3 ). (pnas.org)
  • The protein factors required for this process have been identified, but the molecular steps by which telomere replication takes place are poorly understood. (wellcome.ac.uk)
  • In human somatic cells, cell divisions are accompanied with progressive telomere length shortening due to lack of or insufficient telomerase activity (termed the end-replication problem). (utsouthwestern.edu)
  • However, because of DNA replication mechanisms and because TERT expression is repressed in many types of human cells, the telomeres of these cells shrink a little bit every time a cell divides although in other cellular compartments which require extensive cell division, such as stem cells and certain white blood cells , TERT is expressed and telomere length is maintained. (bionity.com)
  • There are theories that the steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence and in the prevention of cancer . (bionity.com)
  • This is known as the telomere replication problem. (mdpi.com)
  • In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. (mdpi.com)
  • Coulon, S. Solving the Telomere Replication Problem. (mdpi.com)
  • Maestroni L, Matmati S, Coulon S. Solving the Telomere Replication Problem. (mdpi.com)
  • Telomeres, repetitive DNA regions of hexanucleotide repeats, protect chromosomal ends from deterioration during DNA replication. (qiagen.com)
  • The Human Telomeres & Telomerase RT² Profiler PCR Array profiles the expression of 84 key genes central to telomere replication and maintenance. (qiagen.com)
  • However, during each round of replication, some telomere is lost because polymerases are unable to replicate the extreme ends of genomic DNA. (asbmb.org)
  • As a result of cell replication, telomere length decreases, which means that a measurement of telomere length is an accurate test of someone's biological age and state of health. (privatehealth.co.uk)
  • Previously, Lieberman's lab at Wistar has shown that viral DNA replication and maintenance share some common features with telomeres. (eurekalert.org)
  • Telomeres may serve as a barrier to viral replication," Lieberman said. (eurekalert.org)
  • To escape from the normal limits on proliferative potential, cancer cells must employ a means to counteract the gradual telomere attrition that accompanies semi-conservative DNA replication. (frontiersin.org)
  • Telomere replication is both cell cycle- and developmentally regulated, and its control is likely to be complex. (sciencemag.org)
  • Telomeres protect the chromosome ends from degradation, end-to-end fusion and abnormal recombination and they also promote the end replication. (biomedsearch.com)
  • Telomeres are composed of a DNA component characterized by noncoding repetitive sequences rich in guanine (G) and multiple protein components. (news-medical.net)
  • In 1975-1977, Elizabeth Blackburn, working as a postdoctoral fellow at Yale University with Joseph G. Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends. (wikipedia.org)
  • Telomere sequences vary from species to species, but are generally GC-rich. (bionity.com)
  • Telomeres consist of hexameric nucleotide sequences (TTAGGG in humans) that are repeated hundreds to thousands of times at each extremity of each chromosome. (the-scientist.com)
  • In the late 1970s, Elizabeth Blackburn and Joseph Gall discovered the structure of telomeres-short, highly repetitive noncoding nucleotide sequences-in the ciliated protozoan Tetrahymena . (the-scientist.com)
  • Telomerase plays a key role in maintaining the length of telomere by adding G-rich repeat sequences. (scirp.org)
  • Telomeres contain repeated sequences of DNA that, in normal cells, shorten each time a cell divides. (redorbit.com)
  • Telomeres are long repetitive DNA sequences at the ends of chromosome. (bio-medicine.org)
  • Candida underwent rapid evolutionary divergence with respect to telomere sequences. (biomedsearch.com)
  • Concomitant with the evolutionary divergence of telomere sequences, telomere repeat binding factors and telomerase components have also evolved, leading to differences in their functions and domain structures. (biomedsearch.com)
  • The well-established function of telomerase is the elongation of telomeres, which enable cells to increase their replicative capacity (sometimes even indefinitely). (news-medical.net)
  • In vivo analysis of telomere elongation kinetics shows that telomerase does not act on every telomere in each cell cycle but that it exhibits an increasing preference for telomeres as their lengths decline. (springer.com)
  • Armbruster BN, Linardic CM, Veldman T, Bansal NP, Downie DL, Counter CM (2004) Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1. (springer.com)
  • In their recent study published in The Journal of Biological Chemistry, Cech's team demonstrates that introducing mutations in the TEL patch to disrupt its activity while chemically inhibiting telomerase causes a decrease in proliferation of HeLa cancer cells correlated with a suppression of telomere elongation. (asbmb.org)
  • While the majority of human cancers do this by up-regulating telomerase enzyme activity, most of the remainder use a homologous recombination-mediated mechanism of telomere elongation known as alternative lengthening of telomeres (ALT). (frontiersin.org)
  • Collectively, these findings suggest that HOT1 supports telomerase-dependent telomere elongation. (rcsb.org)
  • Therefore, he said, an important next step will be to determine the cellular mechanism that switches the telomere to the on state so that elongation can occur. (fightaging.org)
  • These findings confirm the idea that TRF1 controls telomere dynamics primarily by affecting telomerase-mediated telomere elongation ( 20 , 21 ). (sciencemag.org)
  • The acquisition of telomere repeats was a cornerstone event in the evolution of eukaryotic nucleus, due to their fundamental roles in chromosome organization and stability of the genome. (news-medical.net)
  • Telomere length homeostasis requires telomerase, a cellular reverse transcriptase, which uses an internal RNA moiety as a template for the synthesis of telomere repeats. (springer.com)
  • There are an additional 100-300 kilobases of telomere-associated repeats between the telomere and the rest of the chromosome. (bionity.com)
  • It has long been presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, because only primer dimer-derived products are expected. (nih.gov)
  • Under circumstances in which cell proliferation continues despite critically short telomeres (usually about a few hundred hexanucleotide repeats), the telomere's protective function is lost. (the-scientist.com)
  • Morin GB (1989) The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. (els.net)
  • Typically, human chromosome ends have 2 - 10 kilobase pairs of detectable telomere repeats depending on the type of tissue, the age of the donor and the replicative history of the cells. (scirp.org)
  • HOT1 directly and specifically binds double-stranded telomere repeats, with the in vivo association correlating with binding to actively processed telomeres. (rcsb.org)
  • TRF2 is a sequence-specific DNA binding protein that binds to the duplex array of TTAGGG repeats at human telomeres and protects chromosome ends from end-to-end fusion ( 14-17 ). (sciencemag.org)
  • However, low expression of telomerase (for example, in some normal fibroblasts) cannot maintain telomere length, but plays a role in maintaining chromosomal structure during each S phase of the cell cycle. (news-medical.net)
  • We are now looking for signaling pathways that affect telomere length in muscle stem cells, so that in principle we can develop drugs to block those pathways and maintain telomere length," Mourkioti said. (eurekalert.org)
  • To support healthy aging, it is essential to maintain telomere length. (ralphs.com)
  • This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. (mdpi.com)
  • Dynamics of human telomeres. (els.net)
  • de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. (nature.com)
  • Well, we start by determining how human telomeres are structured - as in the work described in this post. (fightaging.org)
  • Human telomeres are programmed to lose ∼100 base pairs (bp) per population doubling (PD), resulting in senescence after ∼50 PDs ( 2-4 ). (sciencemag.org)
  • Uncapped telomeres are able to activate the DNA damage response and cause end-to-end fusions, resulting in chromosomal instability, cellular senescence and apoptosis (programmed cell death). (news-medical.net)
  • Short telomeres trigger DNA damage checkpoints, which mediate cellular senescence. (springer.com)
  • The telomere length reserve must be sufficient to avoid premature cellular senescence and the acceleration of age-related disease. (springer.com)
  • Here we provide evidence that psychological stress- both perceived stress and chronicity of stress-is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. (pnas.org)
  • In vitro , when telomeres shorten sufficiently, the cell is arrested into senescence. (pnas.org)
  • Cells age if the telomeres are shortened, but when "telomerase activity is high, telomere length is maintained, and cellular senescence is delayed," the Nobel citation noted. (medpagetoday.com)
  • In many cell types, telomeres also serve as biological countdown clocks, being shortened with every cell division until their reduced length triggers the death of the cell or an inactive, non-dividing state called senescence. (eurekalert.org)
  • But some scientists, including Mourkioti, have suspected that in muscular dystrophy the continuous cycles of muscle damage and repair--requiring near-constant cell division for the muscle stem cells--soon erode the regenerative capacities of muscle stem cells, by shortening their telomeres and inducing early death or senescence. (eurekalert.org)
  • Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. (mdpi.com)
  • Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. (nih.gov)
  • The discovery that critical telomere shortening initiates replicative senescence triggered a vast body of epidemiological studies exploring its implications for human aging. (ahajournals.org)
  • There is mounting evidence to suggest that when the telomere shortens to a critical length, cell senescence is triggered. (wiley.com)
  • At the end of cellular replicative lifespan, uncapped telomeres lose this protective mechanism and DNA-damage signalling pathways are triggered that activate p53 and thereby induce replicative senescence. (nature.com)
  • Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. (nature.com)
  • Feldser, D. M. & Greider, C. W. Short telomeres limit tumor progression in vivo by inducing senescence. (nature.com)
  • We already knew that short telomeres play a key role in determining the onset of cellular senescence, but we didn't really understand which features of short telomeres were important. (uni-mainz.de)
  • During aging, telomeres gradually shorten, eventually leading to cellular senescence . (fightaging.org)
  • On the other hand, rampant lengthening of telomeres is also a good way for cancer to get going, since telomeres control the normal process of cell senescence and turnover in cell populations within the body). (fightaging.org)
  • TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. (sciencemag.org)
  • TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. (sciencemag.org)
  • Replicative senescence can be induced by either the p53 or the p16-retino blastoma (RB) pathways ( 4 , 12 , 13 ), but how these pathways are activated in cells with shortened telomeres is not known. (sciencemag.org)
  • TERRA is an RNA species that accumulates specifically at the ends of critically short telomeres by binding directly to the DNA and signals to the cell that these telomeres should be repaired, allowing the cell to carry on dividing. (uni-mainz.de)
  • But the more popular view, to which I subscribe, is that cells which don't express telomerase never divide in the body often enough to get critically short telomeres anyway, in anything like a normal lifetime, unless and until they've already acquired most of the mutations needed for becoming cancerous. (fightaging.org)
  • Inadequate telomere repair and accelerated telomere attrition can be molecular causes of these diseases, and targeting these processes may lead to the development of novel therapies. (the-scientist.com)
  • Moreover, Mendelian randomization studies point to a causal role for shorter telomere length in ACVD, lending support to the hypothesis that the protective antitumor mechanism elicited by critical telomere attrition may act at the expense of unsuccessful cardiovascular aging. (ahajournals.org)
  • More specifically, 2 competitive hypotheses on the role of telomeres as primary risk factor for ACVD were scrutinized: (1) shorter (inherited) telomeres versus (2) higher telomere attrition rates (Figure). (ahajournals.org)
  • Telomere attrition explains the "Hayflick limit," the number of divisions a cell is capable of undergoing in tissue culture before the cell stops dividing. (the-scientist.com)
  • Telomere attrition could be one of the mechanisms involved in these processes [ 3 ]. (royalsocietypublishing.org)
  • While telomere length (TL) has a relatively large heritable component [ 5 ], shorter TL and increased telomere attrition have been linked to stressful conditions during development and disease [ 6 , 7 ]. (royalsocietypublishing.org)
  • However, we still know very little about how an animal's environment per se affects TL and telomere attrition [ 11 ]. (royalsocietypublishing.org)
  • and the rate of attrition of telomere length has been linked to exposure to high oxidative stress and inflammation, both of which are considered important drivers of biological ageing. (bmj.com)
  • Progressive cardiomyocyte apoptosis and telomere attrition were also found. (wellnessresources.com)
  • EGCG, quercetin and carvedilol could prevent telomere attrition and telomere repeat-binding factor 2 (TRF(2)) loss remarkably, whereas captopril and losartan had no effect on oxidative stress and telomere signal. (wellnessresources.com)
  • Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy. (wellnessresources.com)
  • These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. (pnas.org)
  • Thus, telomere length can serve as a biomarker of a cell's biological (versus chronological) "age" or potential for further cell division. (pnas.org)
  • Recent data presented at the11th Annual AACR International Conference on Frontiers in Cancer Prevention Research revealed shortened telomeres - a biomarker linked to aging - and depression significantly reduced bladder cancer patients' survival. (mdanderson.org)
  • Telomere length has emerged as a leading biomarker of aging, and predicts early onset of cardiovascular disease. (scienceblog.com)
  • Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. (hindawi.com)
  • We reciprocally cross-fostered urban and rural nestling great tits ( Parus major L.) to study how growing up in an urban versus rural habitat affected telomere length (TL)-a suggested biomarker of longevity. (royalsocietypublishing.org)
  • So an eventual diagnostic test that searches for the shortened telomere biomarker would be beneficial to diagnostics and help boost chances of a definitive diagnosis, which in turn can facilitate a more personalized treatment plan. (fiercebiotech.com)
  • Understanding this pattern of telomere growth may mean it can be a predictive biomarker for cancer," said Dr. Lifang Hou, the lead study author and a professor of preventive medicine at Northwestern University Feinberg School of Medicine. (medicalxpress.com)
  • The telomerase enzyme, which is a ribonucleoprotein with reverse transcriptase activity, is composed of two main parts - a telomere RNA component and a telomere reverse transcriptase. (news-medical.net)
  • The telomerase enzyme complex is comprised of TERT (the reverse transcriptase) and TR (the essential RNA component that contains a template for telomere repeat addition). (nih.gov)
  • Telomere resolvase, also known as protelomerase, is an enzyme found in bacteria which contain linear plasmids. (wikipedia.org)
  • Greider was a graduate student when she and and Blackburn identified telomerase, the enzyme that makes telomere DNA. (medpagetoday.com)
  • Telomerase is a naturally occurring enzyme that lengthens telomeres and protects them from shortening. (ralphs.com)
  • Telomere lengthening appears to happen in people, and may be a meaningful phenomenon," said co-author Elizabeth Blackburn , PhD, a professor emeritus at UCSF, president of the Salk Institute for Biological Studies in San Diego and 2009 recipient of the Nobel Prize in Physiology or Medicine for her co-discovery of the telomerase enzyme. (scienceblog.com)
  • Telomeres can grow longer, however, through the action of an enzyme called telomerase, which is especially active in cells that need to keep dividing indefinitely, such as stem cells. (labspaces.net)
  • The G-quadruplex structures of telomere DNA inhibit the function of the telomerase enzyme, so we wanted to understand the mechanical stability of this structure. (labspaces.net)
  • Most cancer cells, naturally prone to divide rapidly, use high amounts of an enzyme called telomerase to keep their telomeres intact. (redorbit.com)
  • While many factors contribute to aging and illness, Dr. Elizabeth Blackburn discovered a biological indicator called telomerase, the enzyme that replenishes telomeres, which protect our genetic heritage. (kfai.org)
  • Telomera by Donnell uses the astragalus plant and this, according to Donnell, works in a somewhat different way by aiding aging cells at the shortened, frayed telomeres, where it raises levels of the enzyme telomerase. (truthinaging.com)
  • Happily, when fighting infections, our T-cells can turn on telomerase enzyme and prevent the telomeres from shortening - unless, of course, you have AIDS. (truthinaging.com)
  • Telomerase also has direct telomere-protective functions ( 6 ). (pnas.org)
  • Telomeres are a protective nucleoprotein structure at each chromosome end. (cdc.gov)
  • It also shows, rather surprisingly, that a substantial number of people had telomere lengthening, and that this appeared to be protective. (scienceblog.com)
  • The findings, which will be published in the Dec. 24 edition of the journal Cell Reports , show that this manipulation of telomeres may explain how viruses like herpes are able to successfully replicate while also revealing more about the protective role that telomeres play against other viruses. (eurekalert.org)
  • Their natural protective role is not the only thing that can shorten telomeres, they can also be shortened by genetics and unhealthy lifestyle choices. (worldhealth.net)
  • Over a cell's lifetime, telomeres get gradually shorter with each cell division and therefore the protective cap becomes less and less effective. (uni-mainz.de)
  • A distinct pattern in the changing length of blood telomeres, the protective end caps on our DNA strands, can predict cancer many years before actual diagnosis, according to a new study from Northwestern Medicine in collaboration with Harvard University. (medicalxpress.com)
  • An overhang may be required to form a potentially protective structure at telomeres, the t loop, in which the G strand invades the duplex part of the telomere ( 10 , 11 ). (sciencemag.org)
  • The data presented here argue against this view and suggest that the main event heralding the end of the replicative life of primary human cells is a failure in the protective function of critically shortened telomeres. (sciencemag.org)
  • The telomeres are special structures on the chromosome ends that are essential for providing protection from enzymatic end-degradation and maintaining chromosomal and genomic stability. (news-medical.net)
  • Telomeres are considered as localized structures at the chromosomal ends, they can also be found at internal positions. (news-medical.net)
  • The properties of the eukaryotic telomeres are usually identified as the "capping function", with a principal mission to protect chromosome ends from DNA degradation, DNA repair mechanism and fusion with other chromosomal ends. (news-medical.net)
  • Telomeres are DNA-protein complexes that cap chromosomal ends, promoting chromosomal stability. (pnas.org)
  • Genetic factors, e.g. sex chromosomal inactivation, and non-genetic factors, e.g. antioxidant properties of oestrogen, have been suggested as possible explanations for these sex-specific telomere inheritance and telomere length differences. (nih.gov)
  • This prevents chromosomal fraying and prevents the ends of the chromosome from being processed as a double strand DNA break, which could lead to chromosome-to-chromosome telomere fusions. (bionity.com)
  • We propose that Cdc13p and Ku structurally inhibit recombination at telomeres and that Tel1p regulates the chromosomal cap, acting through Cdc13p. (genetics.org)
  • Uncapped telomeres also result in chromosomal fusions. (wikidoc.org)
  • p53 deletion impairs clearance of chromosomal-instable stem cells in aging telomere-dysfunctional mice. (nature.com)
  • Telomere uncapping or chromosomal free end causes a potential threat to the genomic stability and thus leads to the accumulation of chromosomal abnormalities that have been known to play a role in aging and cancer. (scirp.org)
  • Telomere plays an indispensable role in protecting the chromosomal ends from fusion and degradation. (scirp.org)
  • Chromosomal instability caused due to telomere loss is directly linked with apoptosis (Programmed cell death) as illustrated in Figure 1 . (scirp.org)
  • Because telomere loss causes the kinds of chromosomal changes associated with cancer and aging, an understanding of telomere biology has medical relevance. (sciencemag.org)
  • Telomeres are complex nucleoprotein structures that are crucial for the maintenance of chromosomal integrity ( 3 ). (aacrjournals.org)
  • We present evidence here that a rather recent nonhomologous recombination event in the B. burgdorferi strain Sh-2-82 lineage has replaced its right chromosomal telomere with a large portion of the linear plasmid lp21, which is present in the strain B31 lineage. (asm.org)
  • At least two successive rounds of addition of linear plasmid genetic material to the chromosomal right end appear to have occurred at the Sh-2-82 right telomere, suggesting that this is an evolutionary mechanism by which plasmid genetic material can become part of the chromosome. (asm.org)
  • 53,54 In the animal kingdom, though, long-lived species often have shorter telomeres than do short-lived species, indicating that telomere length probably does not determine life span. (scientificamerican.com)
  • The budding yeast Saccharomyces cerevisiae is the most well-studied model system with regard to telomere and telomerase regulation. (biomedsearch.com)
  • Thus, the comparative analysis of the telomeres and telomerase-related factors in the budding yeast has provided a better understanding on both conserved and variable aspects of telomere regulation. (biomedsearch.com)
  • In recent years, novel insight into the regulation of telomerase at chromosome ends has increased our understanding on how telomere length homeostasis in telomerase-positive cells is achieved. (springer.com)
  • This is new and complex science, but in a nutshell telomeres allow cells to distinguish chromosome ends from broken DNA and they shorten every time a cell divides. (truthinaging.com)
  • While comparisons across studies of telomere length in base pairs are commonly done, it is not highly accurate. (cdc.gov)
  • Only a few risk factors for accelerated shortening have been identified because there have been few studies of telomere length conducted with infants and young children. (parentsguidecordblood.org)
  • Studies of telomere length at birth are needed so that we can better understand risk factors for development of chronic disease, particularly in high-risk populations. (parentsguidecordblood.org)
  • Each time a cell divides, the telomeres become shorter because the telomerase is not very efficient at reading the DNA sequence all the way to the end. (nih.gov)
  • Telomeres shorten every time a cell divides. (medicalxpress.com)
  • PHILADELPHIA - For the first time, researchers have found a link between long telomeres and an increased risk for colorectal cancer, according to research presented at the American Association for Cancer Research special conference on Colorectal Cancer: Biology to Therapy, held here Oct. 27-30, 2010. (mdtmag.com)
  • On the other hand, patients with low levels of depression - as indicated by the Center for Epidemiologic Studies Depression Scale (CES-D) - and long telomeres lived longer. (mdanderson.org)
  • When they discovered that the pattern of cyclic TERRA accumulation was different between short and long telomeres, they knew they were on to something and joined forces for this project. (uni-mainz.de)
  • The length of the shortest telomere represents a much better indicator of cellular aging than the average telomere length, since cells either die or become senescent once the shortest telomeres are depleted. (news-medical.net)
  • The longest telomeres overall had 33 percent likelier odds of developing any cancer, more than the shortest telomeres. (rdmag.com)
  • A U-shaped risk curve still existed, incorporating more cancer risk from the shortest telomeres. (rdmag.com)
  • The shortest telomeres had 63 percent more risk for stomach cancer, 72 percent increase for bladder cancer, 115 percent greater odds for leukemia than those in the middle of the curve. (rdmag.com)
  • Telomeres are associated with biological aging because with each cell division, they divide and get shorter, so that elderly adults have the shortest telomeres. (parentsguidecordblood.org)
  • The mechanism of these telomerase functions is still not completely clear, as it may or may not be linked to maintenance of telomere length. (news-medical.net)
  • In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue. (pnas.org)
  • The telomere prevents this problem by employing a different mechanism to synthesize DNA at this point, thereby preserving the sequence at the terminal of the chromosome. (bionity.com)
  • and 2) the mechanism of telomere size maintainence (e.g. (bio.net)
  • 1 Yet, consensus is lacking on the mechanism underlying the presumed associations between shorter telomeres, atherosclerosis, and ACVD. (ahajournals.org)
  • Emerging evidence supports telomere length as a correlate and potential mechanism underling rates of diseases. (hindawi.com)
  • Work over the past several decades has revealed an active, though limited, mechanism for the normal enzymatic repair of telomere loss in certain proliferative cells. (the-scientist.com)
  • So far, the mechanism of telomere lengthening is unknown, the authors say. (scienceblog.com)
  • The vast majority of human cancers utilize a telomere maintenance mechanism to compensate for the gradual telomere shortening that accompanies cellular proliferation, and thereby obtain an unlimited replicative capacity. (frontiersin.org)
  • These data suggest that while some form of ALT activity may constitute a natural aspect of telomere biology, the mechanism may become dysregulated during cancer development. (frontiersin.org)
  • However, telomere shortening is also a defense mechanism against cancer because highly proliferative cells can only divide when their telomeres do not shorten. (uni-mainz.de)
  • This mechanism ensures the subsequent repair of the short telomere, which is crucial for the cell to survive and keep dividing. (uni-mainz.de)
  • One of the engineering methods required for Aubrey de Grey's proposed methodology of reversing aging is lengthening telomeres , since the gradual shortening of telomere length with age is apparently a mechanism by which cancer becomes more common in older people . (fightaging.org)
  • Most notably, in vitro , oxidative stress can shorten telomeres and antioxidants can decelerate shortening ( 9 , 10 ). (pnas.org)
  • Given these observed links, we hypothesized that chronic psychological stress may lead to telomere shortening and lowered telomerase function in peripheral blood mononuclear cells (PBMCs) and to oxidative stress. (pnas.org)
  • CONCLUSIONS: Pressure overload induced cardiac hypertrophy initiates oxidative stress, induces telomere repeat-binding factor 2 loss and accelerates telomere shortening in hypertrophic myocardium. (wellnessresources.com)
  • The fact that Latina women with at least a high school diploma were more likely to have babies with longer telomere length suggests that education may be a good marker for exposures to oxidative stress. (parentsguidecordblood.org)
  • In a longitudinal study, both leukocyte telomere length and carotid atherosclerosis were quantified in 154 subjects at baseline and after a 9.5-year follow-up, and their interrelation was evaluated. (ahajournals.org)
  • The researchers measured peripheral blood leukocyte DNA telomere length in 772 patients diagnosed with microsatellite stable colorectal cancer. (mdtmag.com)
  • Accumulating evidence supports leukocyte telomere length (LTL) as a biological marker of cellular aging. (hindawi.com)
  • The aim of the current study was to examine the associations of sleep duration and sleep quality with leukocyte telomere length (LTL) in a sample of healthy women in midlife. (hindawi.com)
  • Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999-2000. (cdc.gov)
  • The researchers measured patients' leukocyte telomere length at the start of the study and again five years later, and then examined whether the difference between these measurements predicted which patients were most likely to die over the next four years. (scienceblog.com)
  • In one of the studies, " High Phobic Anxiety is Related to Lower Leukocyte Telomere Length in Women ," led by Olivia Okereke of Harvard University, the researchers compared telomere length with anxiety levels for 5,243 women between the ages of 42 and 69, and found that higher anxiety was generally associated with shorter telomere length. (plos.org)
  • 2012) High Phobic Anxiety Is Related to Lower Leukocyte Telomere Length in Women. (plos.org)
  • The telomere is a nucleoprotein structure comprising the terminal section of a eukaryotic chromosome. (uniprot.org)
  • 55,56,57 Solid scientific evidence has shown that telomere length plays a role in determining cellular life span in normal human fibroblasts and some other normal cell types. (scientificamerican.com)
  • 59,60 Thus, although telomere shortening may play a role in limiting cellular life span, there is no evidence that telomere shortening plays a role in the determination of human longevity. (scientificamerican.com)
  • Recent research points to the crucial roles of telomeres and telomerase in cellular aging and potentially in disease. (pnas.org)
  • Cellular environment also plays an important role in regulating telomere length and telomerase activity. (pnas.org)
  • Cellular aging is the process by which a ell becomes old and dies due in large part to the shortening of its telomeres. (ralphs.com)
  • however, this work has not extended to markers of cellular aging, such as telomere length. (hindawi.com)
  • Scientists at Johns Hopkins have provided more clues to one of the least understood phenomena in some cancers: why the "ends caps" of cellular DNA, called telomeres, lengthen instead of shorten. (redorbit.com)
  • Our finding that Latino children already have shorter telomeres at birth if their mothers did not minimally have a high school education suggests that children may be impacted at the cellular level by maternal access to education. (parentsguidecordblood.org)
  • It turns out that human telomere structure is quite different from that of yeast (that researchers had previously been using as a conceptual model for understanding human cellular mechanisms). (fightaging.org)
  • A schematic drawing that illustrates the typical range of telomere lengths by age in, for example, peripheral blood lymphocytes. (nih.gov)
  • The technique can be used with a microscope and electronic imaging equipment to measure the lengths of telomeres within individual stem cells. (eurekalert.org)
  • Other non-stem muscle cells in the DMD patients had normal telomere lengths. (eurekalert.org)
  • Overall, the individuals with the shortest and the longest telomere lengths were at an increased risk for colorectal cancer, Boardman said. (mdtmag.com)
  • In order to determine if these subsets of patients with younger-onset colorectal cancer have tumors that are mechanistically distinct, we are in the process of comparing the telomere lengths in the peripheral blood DNA with that in the tumor. (mdtmag.com)
  • When a cell's telomeres shorten to critical lengths, the cell senesces. (the-scientist.com)
  • Using the quantitative fluorescence in situ hybridization (Q-FISH) method for telomere measurement, we were able to measure the telomere lengths of various cell types within tissues. (wiley.com)
  • Our Q-FISH method using our original software program "Tissue Telo" is excellent for measuring telomere lengths using tissue sections and PNA probes. (wiley.com)
  • We're collecting about 100,000 telomere lengths in saliva samples and then looking at how those relate to both the extensive longitudinal clinical records that Kaiser is collecting and the genome sequence variations. (scientificamerican.com)
  • What do the telomere lengths of white blood cells, which are dividing cells, tell us about what's happening in non-dividing cells, such as heart-muscle cells? (scientificamerican.com)
  • This suggests that there may be two different mechanisms that affect telomere length and that set up susceptibility to cancer," she said. (mdtmag.com)
  • In future studies, researchers will examine the telomere maintenance genes in the peripheral blood DNA. (mdtmag.com)
  • In a study published online June 30 in Science Express, the Johns Hopkins researchers say they have identified two genes that, when defective, may cause these telomere elongations. (redorbit.com)
  • Without telomeres, the cell division-related shortening could snip off a cell's genes and disrupt key cell functions. (redorbit.com)
  • Finding the genes responsible for alternative lengthening of telomeres is the first step in understanding this process and provides opportunities to develop new drug therapies," says Nickolas Papadopoulos, Ph.D., associate professor at the Johns Hopkins Kimmel Cancer Center and director of translational genetics at Johns Hopkins' Ludwig Center. (redorbit.com)
  • Following a hunch, Meeker and his colleagues took a closer look at the two genes and their specific role in telomere lengthening. (redorbit.com)
  • Although the Johns Hopkins team does not yet have an explanation for how the genes do their lengthening work in cancer, Meeker speculates that the mutations alter the way that telomere DNA is packaged, exposing those areas to instability. (redorbit.com)
  • If the correlation holds up, we could use alternative lengthening of telomeres and ATRX/DAXX mutations as a method of determining a patient's prognosis in addition to developing treatments that target these genes," says Meeker. (redorbit.com)
  • The story explains that telomeres at normal length help keep genes stable, and also that the DNA damage in luminal progenitor cells and their shortened telomeres may very well be ground zero to the development of breast cancer. (fiercebiotech.com)
  • By contrast, the length of telomeres in a patient's own white blood cells, as measured before transplantation, was not associated with survival. (cancer.gov)
  • The average length of telomeres. (yeastgenome.org)
  • By measuring the mean length of telomeres of WBCs from patients with IDDM, we tested the concept that telomeres might play a role in IDDM. (diabetesjournals.org)
  • In addition, nucleolytic activities contribute to telomere erosion. (springer.com)
  • These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation. (hindawi.com)
  • It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening. (sigmaaldrich.com)
  • Telomeres are extended by telomerases , part of a protein subgroup of specialized reverse transcriptase enzymes known as TERT ( TE lomerase R everse T ranscriptases) that are involved in synthesis of telomeres in humans and many other, but not all, organisms. (bionity.com)
  • In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. (nih.gov)
  • Telomerase, which is composed of both an enzymatic subunit (TERT) and an RNA component, promotes genomic stability by lengthening telomeres that have become shortened and is particularly important for stem cell renewal and tumor cell survival. (sciencemag.org)
  • The amount of telomerase present in a cell is key to telomere maintenance, and many transcription factors both positively and negatively regulate the transcription of Tert (see the Perspective by Greider). (sciencemag.org)
  • Telomerase (TERT), a reverse transcriptase, forms a complex with an RNA template and cofactors to extend telomeres. (qiagen.com)
  • Telomerase (TERT) is a reverse transcriptase that employs a small RNA molecule (TERC) as a template to extend telomeres in cells. (the-scientist.com)
  • Aware of this malfunction's destructive impact, researchers from the Collaborative Oncological Gene-environment Study (COGS) consortium, are studying how the gene regulating telomeres - called TERT - contributes to the development of breast and ovarian cancers. (cityofhope.org)
  • The authors write in their paper that "this study provides definitive evidence for genetic control of telomere length by common genetic variants in the TERT locus. (cityofhope.org)
  • Additionally, they write: "Our results show that the relationships between TERT genotype, telomere length and cancer risk are complex and that the TERT locus may influence cancer risk through multiple mechanisms. (cityofhope.org)
  • Although no significant alteration of telomerase reverse transcriptase (TERT) mRNA was found till 7weeks after aortic constriction, progressive upregulation of p53, c-myc and downregulation of bcl-2, telomere repeat-binding factor 2(TRF(2)) were seen. (wellnessresources.com)
  • Factors that recruit telomerase to telomeres in a cell cycle-dependent manner have been identified in Saccharomyces cerevisiae . (springer.com)
  • In humans, telomerase assembles with telomeres during S phase of the cell cycle. (springer.com)
  • The report that `Dolly' 8 the sheep, the first clone from an adult mammal, inherited shortened telomeres from her cell donor and that her telomeres were further shortened by the brief culture of donor cells has raised serious scientific and public concerns about the `genetic age' and potential developmental problems of cloned animals. (nature.com)
  • This study was the first to evaluate donor cell telomere length and outcomes after HCT in SAA. (cancer.gov)
  • In this study, Shahinaz Gadalla, M.D., Ph.D., of NCI's Division of Cancer Epidemiology and Genetics, and her colleagues evaluated associations between pre-HCT white blood cell telomere length among 330 transplant recipients and their matched unrelated donors and survival after an HCT. (cancer.gov)
  • The association between donor cell telomere length and patient survival remained statistically significant after adjusting for donor age and other factors important in SAA-related transplant outcomes. (cancer.gov)
  • The results of this study suggest that donor white blood cell telomere length may have a role in long-term post-transplant survival. (cancer.gov)
  • This novel approach will allow me to use biochemical and biophysical techniques to unpick the individual steps required to copy and reassemble telomeres' each cell cycle. (wellcome.ac.uk)
  • If that were correct, the rate of telomere shortening would only be around 8-10 bp per cell division (RNA primer size ÷ 2 = (16 ~ 20 nt) ÷ 2). (utsouthwestern.edu)
  • Nevertheless, telomerase negative human cells show telomere shortening rates of ~60-70 bp per cell division. (utsouthwestern.edu)
  • In a study published today online in Stem Cell Reports , researchers found that stem cells in the muscles of muscular dystrophy patients may, at an early age, lose their ability to regenerate new muscle, due to shortened telomeres. (eurekalert.org)
  • We found that in boys with DMD, the telomeres are so short that the muscle stem cells are probably exhausted," said the study's senior author, Foteini Mourkioti, PhD, an assistant professor of Orthopaedic Surgery and Cell and Developmental Biology, and co-director of the Musculoskeletal Regeneration Program in the Penn Institute for Regenerative Medicine. (eurekalert.org)
  • To enable their discovery in DMD patients, Mourkioti and colleagues developed a new stem cell telomere-measuring method, based on an existing technique called fluorescence in situ hybridization (FISH). (eurekalert.org)
  • if it were not for telomeres, this would quickly result in the loss of vital genetic information , which is needed to sustain a cell 's activities. (bionity.com)
  • This is because the telomeres act as a sort of time-delay "fuse", eventually running out after a certain number of cell divisions and resulting in the eventual loss of vital genetic information from the cell's chromosome with future divisions. (bionity.com)
  • We report that children and adult telomerase mutation carriers with short telomere length (TL) develop a T cell immunodeficiency that can manifest in the absence of bone marrow failure and causes life-threatening opportunistic infections. (jci.org)
  • T cell receptor excision circles (TRECs) were also undetectable or low, suggesting that newborn screening may identify individuals with germline telomere maintenance defects. (jci.org)
  • Short telomere T cells upregulated DNA damage and intrinsic apoptosis pathways, while older adult T cells upregulated extrinsic apoptosis pathways and programmed cell death 1 (PD-1) expression. (jci.org)
  • When you examine the cell in culture, you find that well, the telomere shortens when you add a stressor like free radicals, hydrogen peroxide when you buffer that environment with an antioxidant like Vitamin C, you don't get the shortening. (sharecare.com)
  • So we know Telomeres is a double edged sword, if it's a cancer cell you don't want it to be high, if it's one of our typical aging cells, you want it to be high. (sharecare.com)
  • Because DNA can only be synthesized in one direction, the RNA primers at the chromosome's ends cannot be filled in, and thus a small amount of DNA is lost with every cell division-a loss that occurs in the telomeres. (the-scientist.com)
  • During normal aging of an animal or in cell culture, cells divide and telomeres shorten. (the-scientist.com)
  • When telomeres become critically short, the cell becomes senescent-it ceases to divide-or undergoes apoptosis-it dies. (the-scientist.com)
  • Telomerase-dependent telomere repair occurs naturally in some cells, such as embryonic and adult stem cells and some cells of the immune system-cell types that divide regularly to support development, maintain tissues, and combat infections, respectively. (the-scientist.com)
  • This phenomenon is considered to be associated with the reduction in telomere length as an indicator of the number of cell divisions undergone. (wiley.com)
  • Eventually, the telomeres become so short that the cell can no longer divide-leading to telomere-related diseases (e.g., blood diseases such as dyskeratosis congenita). (nih.gov)
  • Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. (nature.com)
  • Nalapareddy, K., Jiang, H., Guachalla Gutierrez, L. M. & Rudolph, K. L. Determining the influence of telomere dysfunction and DNA damage on stem and progenitor cell aging: what markers can we use? (nature.com)
  • Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. (nature.com)
  • We know that telomeres play a very important part in the lifespan of a cell," said Paul M. Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor and Professor and Program Leader of the Gene Expression and Regulation Program at The Wistar Institute. (eurekalert.org)
  • But small portions of telomere DNA are lost with each cell division, eventually resulting in cell death. (rdmag.com)
  • However, telomeres are not able to shorten protectively indefinitely, once they reach a certain length, the cell can no longer divide. (worldhealth.net)
  • Telomeres are vital for our survival as the also protect against uncontrolled cell division that leads to cancer, making finding ways to extend or prolong their length important. (worldhealth.net)
  • The loss of telomere is normal in cell division and as such after 20 - 40 divisions, telomere becomes too short to facilitate the capping function. (scirp.org)
  • Also, telomeres normally shorten with each cell division until they reach their limit, causing cell death. (labmanager.com)
  • The team used their probe to observe telomere dynamics during different phases of cell division and to gauge telomere length by measuring the fluorescence intensity. (labmanager.com)
  • If telomeres are up for one cell type, they're up for others overall. (scientificamerican.com)
  • Telomere shortening and reduced cell division are considered a hallmark of ageing and likely contribute to the ageing process. (uni-mainz.de)
  • When a telomere accidentally gets cut short early in a cell's lifetime, it needs to be fixed so that the cell doesn't become senescent too early. (uni-mainz.de)
  • Luke and his lab were interested in understanding how the cell recognizes these shortened and damaged telomeres that have lost their caps. (uni-mainz.de)
  • What we have found with TERRA is an intricate regulatory system that explains how short telomeres are identified by the cell', said Luke. (uni-mainz.de)
  • Chapters in this volume cover telomere structure and function in a range of organisms, focusing on how they are maintained, their roles in cell division and gene expression, and how deficiencies in these structures contribute to cancers and other diseases and even aging. (cshlpress.com)
  • Telomeres (red area) protect the ends of the chromosome and play a key role in cell aging. (sciencephoto.com)
  • When the telomere reaches a certain length the cell stops dividing and dies. (sciencephoto.com)
  • Scientists have been trying to understand how blood cell telomeres , considered a marker of biological age, are affected in people who are developing cancer. (medicalxpress.com)
  • The older you are, the more times each cell in your body has divided and the shorter your telomeres. (medicalxpress.com)
  • Since DNA is responsible for every cell in our body, telomeres play a vital role in our health. (vitamindcouncil.org)
  • Therefore, researchers have begun hypothesizing that vitamin D may help prevent the shortening of telomeres through its regulatory role in cell division. (vitamindcouncil.org)
  • This is something that could keep the cell from making telomeres all day long," he said. (fightaging.org)
  • The telomeres themselves don't contain any crucial information, but they protect the important parts of the chromosome from deterioration by slowly sacrificing themselves, a bit at a time, during each cell division. (plos.org)
  • But what really caught Matt's attention and piqued my interest was that it features a botanical active called astragalus that is supposed to act on the telomeres and extend cell life. (truthinaging.com)
  • In 2008, a UCLA AIDS Institute study has found that a chemical from the astragalus root, frequently used in Chinese herbal therapy, can prevent or slow this progressive telomere shortening, Apparently, a great deal of cell division must take place within the immune system for the system to function properly. (truthinaging.com)
  • Azzalin CM, Redon S, Lingner J (2005) S. cerevisiae Est1/H. sapiens SMG6 protein family members function in telomere metabolism. (springer.com)
  • Baumann P, Cech T (2001) Pot1, the putative telomere end-binding protein in fission yeast and humans. (springer.com)
  • For example, proteomic, genomic, and molecular approaches have afforded us unprecedented insight into the complex protein interaction networks at work on the telomere chromatin and the detailed information regarding telomere dynamics in response to stress or stimuli. (springer.com)
  • The TPP1 protein of the telomere exhibits a patch of amino acids on its surface called the TEL patch. (asbmb.org)
  • said nucleotide sequence characterized in coding for an protein that regulates telomere length or modulates telomerase activity and is present in human or mammalian cells that expresses telomerase activity. (google.com)
  • Almost 85% of tumor cells compensate for telomere loss aided by telomerase-associated protein complex and shelter in complex or telosome. (scirp.org)
  • In search for such a factor we carried out a SILAC-based DNA-protein interaction screen and identified HMBOX1, hereafter referred to as homeobox telomere-binding protein 1 (HOT1). (rcsb.org)
  • In the new study, Whooley and colleagues asked whether the rate of telomere change - rather than absolute telomere length - might be a better predictor of health span in heart disease patients. (scienceblog.com)
  • Add this to the approximately 8 billion benefits of omega-3 fatty acids: They could help preserve DNA segments known as telomeres, whose degradation is a key marker of aging. (aarp.org)
  • Thus, TRF1 and TRF2 both act as negative regulators of telomere length but affect different aspects of telomere dynamics. (sciencemag.org)
  • Since their discovery in the mid-1980s, biology of telomeres attracted significant interest from the scientific community due to their aforementioned importance. (news-medical.net)
  • My work will provide fundamental molecular insights into the biology of telomeres, which will help us better understand human diseases such as cancer. (wellcome.ac.uk)
  • This assay will facilitate investigations of the biology of telomeres and the roles they play in the molecular pathophysiology of diseases and aging. (nih.gov)
  • Flowchart representing the relationship between telomere loss and apoptosis. (scirp.org)
  • These variations were not observed in cord blood leukocytes, which imply different telomere homeostasis mechanisms in fetal cord blood. (mendeley.com)
  • We have recently found that human telomere overhangs in telomerase-negative cells are processed by multiple steps and leading/lagging strands are produced by distinct mechanisms. (utsouthwestern.edu)
  • The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. (nih.gov)
  • Based on their results, the investigators now propose that telomeres also modulate the behavior of cells by controlling gene expression, by as yet unknown mechanisms, says Seimiya. (asm.org)
  • Telomeres are usually replicated by telomerase, a telomere-specific reverse transcriptase, although telomerase-independent mechanisms of telomere maintenance exist. (sciencemag.org)
  • This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. (sciencemag.org)
  • Oulton R and Harrington L (2000) Telomeres, telomerase, and cancer: life on the edge of genomic stability. (els.net)
  • Cells that are able to maintain telomeres at a satisfactory length (typically using telomerase) avoid genomic instability and therefore accumulate mutations more slowly. (fightaging.org)
  • This has, as Reason alludes to, been suggested by some people to imply that cells which express plenty of telomerase will be less prone to become cancers than normal cells (which get short telomeres and hence genomic instability if they divide a lot). (fightaging.org)
  • Telomere dynamics are intensively studied in human ageing research and epidemiology, with many correlations reported between telomere length and age-related diseases, cancer and death. (nih.gov)
  • A postdoctoral position is available to investigate telomere dynamics in Saccharomyces cerevisiae in the laboratory of Art Lustig at Tulane University Medical Center. (bio.net)
  • On the other side, telomere shortening suppresses tumor formation through limiting the replicative potential of cells. (springer.com)
  • Although these disorders seem to be clinically diverse, collectively they comprise a single syndrome spectrum defined by the short telomere defect. (nih.gov)
  • Wild-derived inbred mouse strains have short telomeres. (scientificamerican.com)
  • The question remains whether Dolly's short telomeres were an exception or a general fact, which would differ from the telomeres of fetal-derived clones. (nature.com)
  • We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. (pnas.org)
  • A study investigated whether low vitamin D status is associated with short telomeres, since both are linked to risk of chronic health conditions. (vitamindcouncil.org)
  • The team found that telomeres specifically in muscle stem cells are abnormally short in teenage boys with Duchenne Muscular Dystrophy (DMD), as well as in young mice with the same genetic disorder. (eurekalert.org)
  • Telomeres are made of one short sequence of DNA building blocks (TTAGGG) repeated over and over, and the new FISH-based method (MuQ-FISH) uses a fluorescent probe designed to stick specifically to that sequence. (eurekalert.org)
  • If telomeres become too short, they will potentially unfold from their presumed closed structure. (bionity.com)
  • Cancer cells may maintain short telomeres to maintain their undifferentiated state," says Hiroyuki Seimiya, a researcher on the study. (asm.org)
  • Inhibition of telomere extension leads to short telomeres and premature aging-related diseases, whereas uncontrolled telomere lengthening promotes carcinogenesis. (qiagen.com)
  • In fact, the HIV-positive participants' telomeres were as short as that typically found in people who are 20 to 30 years older. (thebody.com)
  • Telomeres have been linked to numerous diseases over the years, but how exactly short telomeres cause diseases and how medicine can prevent telomere erosion are still up for debate. (the-scientist.com)
  • NEW YORK (GenomeWeb) - A team from the Mayo Clinic has examined the genetic and phenotypic features that occurs in individuals diagnosed with short telomere syndrome (STS), a condition resulting in symptoms that range from accelerated aging or bone marrow failure to immune and multiple organ problems. (genomeweb.com)
  • The data collected from 464 patients enrolled in MD Anderson's ongoing epidemiology bladder cancer study, showed a significant increase in mortality for patients who had high levels of depressive symptoms as well as short telomeres. (mdanderson.org)
  • Those with short telomeres and high levels of depression had a three-fold risk of mortality. (mdanderson.org)
  • Now, research by scientists at UC San Francisco and the Veterans Affairs Medical Center in San Francisco has found that change in telomere length over time is also important: heart disease patients whose telomeres shrank over time had a worse short-term prognosis than those whose telomeres stayed stable, and those whose average telomere length grew over the course of the study had a higher chance of survival. (scienceblog.com)
  • The short and long extremes of telomere length significantly increase cancer risk, according to new University of Pittsburgh research to be presented at the American Association for Cancer Research conference in Washington D.C. today. (rdmag.com)
  • Short telomeres have previously been linked to cancer. (rdmag.com)
  • They discovered that an RNA molecule called TERRA helps to ensure that very short (or broken) telomeres get fixed again. (uni-mainz.de)
  • Furthermore, they wanted to determine which factors were important for promoting the repair of short telomeres. (uni-mainz.de)
  • Meanwhile, Arianna Lockhart and Marco Graf were investigating the accumulation of TERRA at short telomeres. (uni-mainz.de)
  • The telomere theory of aging is on the way out , however, and there is some uncertainty as to just what short telomeres mean for health and longevity for any given individual. (fightaging.org)
  • Eventually, telomeres become too short to serve as protection, causing cells to age and stop functioning properly. (vitamindcouncil.org)
  • The short answer: both higher stress and severe exhaustion were found to be correlated with decreased telomere length, with potential implications for aging and long-term health. (plos.org)
  • First, it gives us an indication that some viruses are able to manipulate telomeres specifically in order to replicate. (eurekalert.org)
  • As cells replicate and age the telomere steadily shrinks. (sciencephoto.com)
  • Future therapies that prevent telomere loss and keep muscle stem cells viable might be able to slow the progress of disease and boost muscle regeneration in the patients. (eurekalert.org)
  • Cancer cells are characterized by seemingly indestructible telomeres, whereas some inherited diseases are characterized by defective telomerase, which damages cells. (medpagetoday.com)
  • Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. (mdpi.com)
  • In the older participants, Rickabaugh and her colleagues found that shorter telomeres were associated with low numbers of the type of immune cells needed to mount and sustain an adequate response to HIV and other diseases. (thebody.com)
  • In addition to cancer, telomeres have been found to be involved in numerous other diseases, including liver dysfunction and aplastic anemia, a condition in which the bone marrow does not produce a sufficient supply of new blood cells. (the-scientist.com)
  • Telomere biology diseases are associated with greatly increased predisposition to a variety of cancers, including leukemia and head/neck cancer. (chop.edu)
  • Consensus guidelines recommend that patients with telomere biology diseases should receive care in expert centers familiar with both the varied manifestations of these diseases, as well as with recommended screening guidelines for cancer and organ dysfunction. (chop.edu)
  • Many aging-related diseases are linked to shortened telomeres. (wikidoc.org)
  • The present invention provides methods and reagents for regulating telomere length and modulating telomerase activity in mammalian cells as well as for detecting, diagnosing, and treating related diseases and conditions in humans and other mammals. (google.com)
  • New research has shown that it may one day be possible to treat people with telomere-related diseases using small molecule compounds that restore telomerase levels to normal levels. (nih.gov)
  • This first-in-class therapeutic lead is an exciting new direction for potential treatment of telomere-related diseases. (nih.gov)
  • Telomere shortening is considered to be a measure of the human biological clock, longer ones indicate a lower risk of certain metabolic diseases and younger cells, but they can also predict a greater risk of certain cancers. (worldhealth.net)
  • If telomeres malfunction, they are unable to maintain chromosome stability, which can lead to diseases such as cancer. (labmanager.com)
  • Being able to visualize telomere length was both surprising and exciting, says Namasivayam, as it can be developed to create an efficient and robust approach for detecting severe telomere shortening in diseases, such as age-related retinal degeneration, with low energy light. (labmanager.com)
  • Researchers, journalists, and inquiring minds want to know more about telomeres, which seem to hold clues to human aging and age-related diseases. (cdc.gov)
  • Although there are different architectures, telomeres in a broad sense, are a widespread genetic feature most commonly found in eukaryotes. (wikipedia.org)
  • People with dyskeratosis congenita, a rare genetic disease that diminishes the ability to synthesize sufficient telomerase, have shortened telomeres and die prematurely from progressive bone marrow failure and vulnerability to infections ( 8 ). (pnas.org)
  • Without telomeres at the end of DNA, this genetic sequence would be deleted and the chromosome would grow shorter and shorter in subsequent replications. (bionity.com)
  • 4 The end-to-end chromosome fusions observed in some tumors could play a role in genetic instability associated with tumorigenesis, and possibly result from telomere loss. (wiley.com)
  • Human telomere length (TL) is affected by genetic and environmental factors. (chiroeco.com)
  • We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. (hindawi.com)
  • The dashed lines represent a typical age range in which these disorders may first manifest, and 'G n ', 'G n + 1 ' and 'G n + 2 ' designate three successive generations manifesting with earlier-onset and evolving disease type owing to progressive telomere shortening. (nih.gov)
  • Statistically, older people have shorter telomeres in their skin and blood cells than do younger people. (scientificamerican.com)
  • In people, telomeres shorten with age in all replicating somatic cells that have been examined, including fibroblasts and leukocytes ( 4 ). (pnas.org)
  • We also detected higher percentage of cells with telomere capture among the diabetic trophoblasts compared to the healthy controls (19.8 ± 5.12% vs. 9.6 ± 3.65%, P = 0.038). (mendeley.com)
  • These results can explain the telomere shortening rate in telomerase negative cells [(lagging strand overhang 110 nt + leading strand overhang 30 nt)÷2 = ~70nt]. (utsouthwestern.edu)
  • The finding of shortened telomeres could help explain why prior research has found defects in the functions of muscle stem cells from muscular dystrophy patients. (eurekalert.org)
  • Due to the DMD, their muscle stem cells are constantly repairing themselves, which means the telomeres are getting shorter at an accelerated rate, much earlier in life. (eurekalert.org)
  • Mourkioti and her team initially used their new technique to show that the telomeres of muscle stem cells are about the same length in healthy lab mice, whether the mice are young or old. (eurekalert.org)
  • In contrast, the scientists found that in young mice with a severe DMD-like disorder as well as in several teenage patients with DMD, muscle stem cells on average had abnormally shortened telomeres. (eurekalert.org)
  • The findings suggest that telomere-shortening specifically in muscle stem cells is a factor in the progressive muscle weakening and wasting seen in muscular dystrophy patients. (eurekalert.org)
  • The findings also point to the possibility that future treatments to block the shortening of telomeres in muscle stem cells might be able to slow or even stop the disease. (eurekalert.org)
  • These studies demonstrated that telomeres-typically measured in the DNA isolated from blood cells-clearly shorten with age. (ahajournals.org)
  • Cancer cells have shorter telomeres compared to healthy cells, but they guard their immortality by maintaining these telomeres' length. (asm.org)
  • If the telomeres shorten, then cells age. (mdtmag.com)
  • When people get older, and their cells have reproduced for many generations, the tips of their mitochondrial DNA snippet of the DNA called telomeres become shorter and more ragged, much like the worn caps at the ends of used shoelaces. (thebody.com)
  • When telomeres degrade like this, the cells don't function or reproduce well. (thebody.com)
  • To further illuminate what is happening with telomeres in HIV-positive people, Tammy Rickabaugh, PhD, and Beth Jamieson, PhD, from UCLA, and their colleagues looked at the effect of telomere length on people's ability to produce and preserve naive CD4 cells that had not previously encountered any pathogens and thus act as a reserve against future infections and cancers. (thebody.com)
  • What's more, when Rickabaugh's team looked at the group responding well to ARV therapy, they found that telomeres were shorter within just a few years of infection and that while naive cells did recover somewhat after starting treatment, they did not do so completely and remained impaired. (thebody.com)
  • This eventually leads to enough erosion of the telomere to cause cells to stop dividing and die off. (asbmb.org)
  • Telomere lengthening in cancer cells, however, confers an abnormal proliferative ability. (the-scientist.com)
  • Some proliferative cells can elongate telomeres enzymatically through the telomerase complex. (the-scientist.com)
  • Using cells from people with dyskeratosis congenita, BCH001 improved telomerase activity and elongated telomeres in cells with PARN mutations. (nih.gov)
  • Remarkably, oral administration of RG7834 reversed telomere shortening in PARN-deficient human blood cells compared to a control. (nih.gov)
  • However, previous studies evaluating telomere length in white blood cells called leukocytes as a predictor of mortality have produced inconsistent findings, only sometimes predicting mortality. (scienceblog.com)
  • However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. (hindawi.com)
  • These findings allow us to ask additional questions and better understand just how telomeres may protect cells from viral infection. (eurekalert.org)
  • Here, we review current findings about telomere structure in ALT cells, including DNA sequence, shelterin content, and heterochromatic state. (frontiersin.org)
  • As cells divide, their telomeres get progressively shorter, until eventually the cells stop dividing. (labspaces.net)
  • The probe, called SiR-TTet59B, binds to telomeres in living cells. (labmanager.com)
  • When the low-intensity near-infrared light is shone on the cells, the silicon-rhodamine fluoresces, showing the telomeres in action. (labmanager.com)
  • Most of your studies look at telomere length in white-blood cells, but you've started looking at cells in saliva. (scientificamerican.com)
  • Yet, some cancer cells are known to maintain their telomere length without help from telomerase. (redorbit.com)
  • With no increased production of telomerase, scientists were left to wonder how cancer cells managed to maintain their telomeres, a phenomenon known as "alternative lengthening of telomeres. (redorbit.com)
  • Fluorescent dyes targeted specifically to telomeres showed "huge aggregates of telomere DNA" in the 25 samples, with each fluorescent spot holding about 100 times more telomere DNA than normal cells, according to Meeker. (redorbit.com)
  • Telomeres naturally shorten with age in all replicating somatic cells unless they are elongated by the activity of telomerase ( 3 ). (aacrjournals.org)
  • As the article notes, stunted telomeres appear to be linked to a number of different cancer cells. (fiercebiotech.com)
  • Late last fall, for example, University of Wisconsin scientists concluded that shortened telomeres in white blood cells pointed to a higher risk of pancreatic cancer. (fiercebiotech.com)
  • In the case of the Indiana University/British Columbia Cancer Agency work, however, they made a similar link by looking at stunted telomeres in luminal progenitor cells. (fiercebiotech.com)
  • What they found, according to the write-up: The shorter telomeres are common in these cells, as is large amounts of DNA damage. (fiercebiotech.com)
  • The patient's telomere value was 73 and is a calculation of the patient's TL derived from nucleated white blood cells obtained from whole blood. (chiroeco.com)
  • Via FuturePundit , news of a study on telomere differences by gender: "This new study [shows] significantly shorter telomeres and higher erosion rates in men than in women, which likely causes a shorter life expectancy of male cells and tissues. (fightaging.org)
  • Without telomeres, DNA becomes damaged, leading to dysfunctional cells. (vitamindcouncil.org)
  • Shortened telomere length in white blood cells of patients with IDDM. (diabetesjournals.org)
  • The enhanced telomere shortening explains previously recorded effects of TRF2 on telomere length maintenance in telomerase-positive cells ( 20 ). (sciencemag.org)
  • thus longitudinal studies measuring actual telomere erosion rates in individuals over times represent more powerful study designs for demonstrating causal effects. (news-medical.net)
  • Kheirollahi M. Telomere, Regulation and Tumorigenesis. (news-medical.net)
  • New and rapid advances in technology have equipped us with a variety of tools and platforms to ask fundamental questions of telomere regulation and have allowed investigators to carry out experiments using diverse model systems. (springer.com)
  • QIAGEN provides a broad range of assay technologies for telomere and telomerase research that enables analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. (qiagen.com)
  • Model of telomere length regulation by TRF1. (els.net)
  • T‐loop model of telomere protection and length regulation. (els.net)
  • In this review, I will discuss telomeres and telomerase-related factors and their functions in telomere and telomerase regulation in C. albicans. (biomedsearch.com)
  • Telomeres naturally shorten with age. (cdc.gov)
  • There has been mounting evidence of a causal role for telomere dysfunction in a number of degenerative disorders. (nih.gov)
  • Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. (nih.gov)
  • We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. (nih.gov)
  • We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. (nih.gov)
  • BACKGROUND: Telomere signaling plays a role in regulating cardiomyocyte apoptosis during cardiac dysfunction. (wellnessresources.com)
  • The telomere-capping complex shelterin protects functional telomeres and prevents the initiation of unwanted DNA-damage-response pathways. (nature.com)
  • This study reveals that p53, a downstream effector of telomere-initiated damage signalling, also functions upstream of the shelterin complex. (nature.com)
  • The Northwestern and Harvard study is believed to be the first to look at telomere length at more than one time point before diagnosis. (medicalxpress.com)
  • Single-nucleotide polymorphisms in two specific areas were strongly associated with telomere length. (cityofhope.org)
  • We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. (sigmaaldrich.com)